178 results on '"Bassem A. Hassan"'
Search Results
2. Induction of granule and Purkinje cells from primary cultured mouse cerebellar progenitors
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Tingting Zhang, Tengyuan Liu, and Bassem A. Hassan
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Cell Biology ,Cell culture ,Microscopy ,Neuroscience ,Stem Cells ,Cell Differentiation ,Science (General) ,Q1-390 - Abstract
Summary: The architecturally stereotypical structure of cerebellum is ideal for investigating the generation of neuronal diversity, but in vitro models for assessing early cerebellar progenitor differentiation were lacking. Here, we report a detailed protocol for long-term in vitro generation of Pax6+ granule cells and Calbindin+ Purkinje cells from common Sox2+ embryonic cerebellar progenitors. We describe the procedure for dissecting mouse cerebellar anlage, cell seeding, and tamoxifen-induced labeling of progenitor cells, followed by time-lapse video recording of clonal expansion and neuronal differentiation.For complete details on the use and execution of this protocol, please refer to Zhang et al. (2021).
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- 2021
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3. Slit/Robo Signaling Regulates Multiple Stages of the Development of the Drosophila Motion Detection System
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Pablo Guzmán-Palma, Esteban G. Contreras, Natalia Mora, Macarena Smith, M. Constanza González-Ramírez, Jorge M. Campusano, Jimena Sierralta, Bassem A. Hassan, and Carlos Oliva
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nervous system development ,cell migration ,axon guidance ,Slit-Robo pathway ,Drosophila melanogaster ,Biology (General) ,QH301-705.5 - Abstract
Neurogenesis is achieved through a sequence of steps that include specification and differentiation of progenitors into mature neurons. Frequently, precursors migrate to distinct positions before terminal differentiation. The Slit-Robo pathway, formed by the secreted ligand Slit and its membrane bound receptor Robo, was first discovered as a regulator of axonal growth. However, today, it is accepted that this pathway can regulate different cellular processes even outside the nervous system. Since most of the studies performed in the nervous system have been focused on axonal and dendritic growth, it is less clear how versatile is this signaling pathway in the developing nervous system. Here we describe the participation of the Slit-Robo pathway in the development of motion sensitive neurons of the Drosophila visual system. We show that Slit and Robo receptors are expressed in different stages during the neurogenesis of motion sensitive neurons. Furthermore, we find that Slit and Robo regulate multiple aspects of their development including neuronal precursor migration, cell segregation between neural stem cells and daughter cells and formation of their connectivity pattern. Specifically, loss of function of slit or robo receptors in differentiated motion sensitive neurons impairs dendritic targeting, while knocking down robo receptors in migratory progenitors or neural stem cells leads to structural defects in the adult optic lobe neuropil, caused by migration and cell segregation defects during larval development. Thus, our work reveals the co-option of the Slit-Robo signaling pathway in distinct developmental stages of a neural lineage.
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- 2021
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4. The CCR4-NOT complex is a tumor suppressor in Drosophila melanogaster eye cancer models
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Carmen Vicente, Rocco Stirparo, Sofie Demeyer, Charles E. de Bock, Olga Gielen, Mardelle Atkins, Jiekun Yan, Georg Halder, Bassem A. Hassan, and Jan Cools
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CCR4-NOT ,Leukemia ,mRNA stability ,Tumor suppressor ,Drosophila melanogaster ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The CNOT3 protein is a subunit of the CCR4-NOT complex, which is involved in mRNA degradation. We recently identified CNOT3 loss-of-function mutations in patients with T-cell acute lymphoblastic leukemia (T-ALL). Methods Here, we use different Drosophila melanogaster eye cancer models to study the potential tumor suppressor function of Not3, the CNOT3 orthologue, and other members of the CCR4-NOT complex. Results Our data show that knockdown of Not3, the structural components Not1/Not2, and the deadenylases twin/Pop2 all result in increased tumor formation. In addition, overexpression of Not3 could reduce tumor formation. Not3 downregulation has a mild but broad effect on gene expression and leads to increased levels of genes involved in DNA replication and ribosome biogenesis. CycB upregulation also contributes to the Not3 tumor phenotype. Similar findings were obtained in human T-ALL cell lines, pointing out the conserved function of Not3. Conclusions Together, our data establish a critical role for Not3 and the entire CCR4-NOT complex as tumor suppressor.
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- 2018
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5. p27Kip1 Modulates Axonal Transport by Regulating α-Tubulin Acetyltransferase 1 Stability
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Giovanni Morelli, Aviel Even, Ivan Gladwyn-Ng, Romain Le Bail, Michal Shilian, Juliette D. Godin, Elise Peyre, Bassem A. Hassan, Arnaud Besson, Jean-Michel Rigo, Miguel Weil, Bert Brône, and Laurent Nguyen
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Biology (General) ,QH301-705.5 - Abstract
Summary: The protein p27Kip1 plays roles that extend beyond cell-cycle regulation during cerebral cortex development, such as the regulation of neuronal migration and neurite branching via signaling pathways that converge on the actin and microtubule cytoskeletons. Microtubule-dependent transport is essential for the maturation of neurons and the establishment of neuronal connectivity though synapse formation and maintenance. Here, we show that p27Kip1 controls the transport of vesicles and organelles along the axon of mice cortical projection neurons in vitro. Moreover, suppression of the p27Kip1 ortholog, dacapo, in Drosophila melanogaster disrupts axonal transport in vivo, leading to the reduction of locomotor activity in third instar larvae and adult flies. At the molecular level, p27Kip1 stabilizes the α-tubulin acetyltransferase 1, thereby promoting the acetylation of microtubules, a post-translational modification required for proper axonal transport. : Morelli et al. report that p27Kip1/Dacapo modulates the acetylation of microtubules in axons via stabilization of ATAT1, the main α-tubulin acetyltransferase. Its conditional loss leads to the reduction of bidirectional axonal transport of vesicles and mitochondria in vitro in mice and in vivo in Drosophila. Keywords: p27Kip1, dacapo, acetylation, axonal transport, ATAT1, alpha-tubulin, HDAC6, Drosophila, mouse, cerebral cortex
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- 2018
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6. A Fat-Facets-Dscam1-JNK Pathway Enhances Axonal Growth in Development and after Injury
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Marta Koch, Maya Nicolas, Marlen Zschaetzsch, Natalie de Geest, Annelies Claeys, Jiekun Yan, Matthew J. Morgan, Maria-Luise Erfurth, Matthew Holt, Dietmar Schmucker, and Bassem A. Hassan
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axonal growth ,axonal injury ,post-transcriptional reguylatiopn ,Central nervous system ,Drosophila melanogaster ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Injury to the adult central nervous systems (CNS) can result in severe long-term disability because damaged CNS connections fail to regenerate after trauma. Identification of regulators that enhance the intrinsic growth capacity of severed axons is a first step to restore function. Here, we conducted a gain-of-function genetic screen in Drosophila to identify strong inducers of axonal growth after injury. We focus on a novel axis the Down Syndrome Cell Adhesion Molecule (Dscam1), the de-ubiquitinating enzyme Fat Facets (Faf)/Usp9x and the Jun N-Terminal Kinase (JNK) pathway transcription factor Kayak (Kay)/Fos. Genetic and biochemical analyses link these genes in a common signaling pathway whereby Faf stabilizes Dscam1 protein levels, by acting on the 3′-UTR of its mRNA, and Dscam1 acts upstream of the growth-promoting JNK signal. The mammalian homolog of Faf, Usp9x/FAM, shares both the regenerative and Dscam1 stabilizing activities, suggesting a conserved mechanism.
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- 2018
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7. Regulation of Adult CNS Axonal Regeneration by the Post-transcriptional Regulator Cpeb1
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Wilson Pak-Kin Lou, Alvaro Mateos, Marta Koch, Stefan Klussman, Chao Yang, Na Lu, Sachin Kumar, Stefanie Limpert, Manuel Göpferich, Marlen Zschaetzsch, Christopher Sliwinski, Marc Kenzelmann, Matthias Seedorf, Carlos Maillo, Elena Senis, Dirk Grimm, Radhika Puttagunta, Raul Mendez, Kai Liu, Bassem A. Hassan, and Ana Martin-Villalba
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axon regeneration ,translation ,polysome profiling ,motif analysis ,CPEB1 ,spinal cord injuries ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Adult mammalian central nervous system (CNS) neurons are unable to regenerate following axonal injury, leading to permanent functional impairments. Yet, the reasons underlying this regeneration failure are not fully understood. Here, we studied the transcriptome and translatome shortly after spinal cord injury. Profiling of the total and ribosome-bound RNA in injured and naïve spinal cords identified a substantial post-transcriptional regulation of gene expression. In particular, transcripts associated with nervous system development were down-regulated in the total RNA fraction while remaining stably loaded onto ribosomes. Interestingly, motif association analysis of post-transcriptionally regulated transcripts identified the cytoplasmic polyadenylation element (CPE) as enriched in a subset of these transcripts that was more resistant to injury-induced reduction at the transcriptome level. Modulation of these transcripts by overexpression of the CPE binding protein, Cpeb1, in mouse and Drosophila CNS neurons promoted axonal regeneration following injury. Our study uncovered a global evolutionarily conserved post-transcriptional mechanism enhancing regeneration of injured CNS axons.
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- 2018
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8. The Fungal Aroma Gene ATF1 Promotes Dispersal of Yeast Cells through Insect Vectors
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Joaquin F. Christiaens, Luis M. Franco, Tanne L. Cools, Luc De Meester, Jan Michiels, Tom Wenseleers, Bassem A. Hassan, Emre Yaksi, and Kevin J. Verstrepen
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Biology (General) ,QH301-705.5 - Abstract
Yeast cells produce various volatile metabolites that are key contributors to the pleasing fruity and flowery aroma of fermented beverages. Several of these fruity metabolites, including isoamyl acetate and ethyl acetate, are produced by a dedicated enzyme, the alcohol acetyl transferase Atf1. However, despite much research, the physiological role of acetate ester formation in yeast remains unknown. Using a combination of molecular biology, neurobiology, and behavioral tests, we demonstrate that deletion of ATF1 alters the olfactory response in the antennal lobe of fruit flies that feed on yeast cells. The flies are much less attracted to the mutant yeast cells, and this in turn results in reduced dispersal of the mutant yeast cells by the flies. Together, our results uncover the molecular details of an intriguing aroma-based communication and mutualism between microbes and their insect vectors. Similar mechanisms may exist in other microbes, including microbes on flowering plants and pathogens.
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- 2014
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9. The Little Fly that Could: Wizardry and Artistry of Drosophila Genomics
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Radoslaw K. Ejsmont and Bassem A. Hassan
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Drosophila ,genetics ,genomics ,Genetics ,QH426-470 - Abstract
For more than 100 years now, the fruit fly Drosophila melanogaster has been at the forefront of our endeavors to unlock the secrets of the genome. From the pioneering studies of chromosomes and heredity by Morgan and his colleagues, to the generation of fly models for human disease, Drosophila research has been at the forefront of genetics and genomics. We present a broad overview of some of the most powerful genomics tools that keep Drosophila research at the cutting edge of modern biomedical research.
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- 2014
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10. Modified Weaver Dunn Versus Ligamentous Reconstruction Grafts in Chronic Acromioclavicular Joint Dislocation: A Systematic Review and Meta-Analysis of Comparative Studies
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Mohammad Daher BSc, Ali Ghoul MD, Charbel Farhat BSc, Peter Boufadel MD, Mohamad Y Fares MD, Bassem El Hassan MD, and Joseph A Abboud MD
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Orthopedic surgery ,RD701-811 - Abstract
Background Acromioclavicular (AC) joint trauma is a frequent sports injury. Modified Weaver Dunn (MWD) is a commonly used technique to address this injury. However, tendinous grafts (Autogenous Palmaris Longus or Semitendinosus tendons) are increasingly being used due to the biologic weakness of MWD. Methods Three search was done until January 2024 with data extraction consisting of adverse events (infections and failures), Constant-Murley score, American Shoulder and Elbow Surgeons score, and postoperative coracoclavicular distance. Results Four studies were included in this metaanalysis. Tendinous graft was shown to have statistically better ASES and Constant-Murley scores. Furthermore, there were no difference in adverse events, and postoperative coracoclavicular distance. Conclusion The tendinous graft showed no differences in adverse events, and postoperative coracoclavicular distance when compared to modified Weaver Dunn. However, it showed higher postoperative ASES and Constant-Murley score without analysis of the minimal clinical important difference making the difference solely statistical. Level of evidence 3.
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- 2024
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11. Correction: Ubiquitin Ligase HUWE1 Regulates Axon Branching through the Wnt/β-Catenin Pathway in a Model for Intellectual Disability.
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Joke Vandewalle, Marion Langen, Marlen Zschaetzsch, Bonnie Nijhof, Jamie M. Kramer, Hilde Brems, Marijke Bauters, Elsa Lauwers, Mohammed Srahna, Peter Marynen, Patrik Verstreken, Annette Schenck, Bassem A. Hassan, and Guy Froyen
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Medicine ,Science - Published
- 2014
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12. Subscapular sparing approach for total shoulder arthroplasty: a systematic review and meta-analysis of comparative studies
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Mohammad Daher, BSc, Ali Ghoul, MD, Mohamad Y. Fares, MD, Joseph Abboud, MD, and Bassem El Hassan, MD
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Subscapularis sparing ,Total shoulder arthroplasty ,Reverse shoulder arthroplasty ,Standard approach ,Limited exposure ,Postoperative range of motion ,Surgery ,RD1-811 - Abstract
Background: Total shoulder arthroplasty has been effective in treating primary glenohumeral arthritis surgically. However, the subscapularis (SSC) tendon must be released as part of the surgery's conventional approach, which could lead to postoperative problems and later tendon failure. Using a procedure that spares the tendon, Lafosse et al reported improved postoperative SSC performance. This meta-analysis will compare this approach to the standard one. Methods: PubMed, Cochrane, and Google Scholar (pages 1-20) were searched till October 2022. The clinical outcomes consisted of the postoperative pain, adverse events, and range of motion. Results: Only 3 studies were included in this meta-analysis. The subscapularis sparing approach tended to have better postoperative internal rotation (P = .06) and shoulder elevation (P = .1); however, the results were marginally statistically insignificant. Conclusion: This is the first meta-analysis to compare the subscapularis sparing to the standard approach in total shoulder arthroplasty. Showing better postoperative range of motion (elevation and internal rotation), the SSC approach might be considered as a good substitute to the standard one. However, it is limited by the potentially limited exposure making it harder to use in muscular and obese patients. More randomized clinical trials are needed to reach more significant results and establish clearer indications of this approach.
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- 2023
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13. A New Behavioral Paradigm for Visual Classical Conditioning in Drosophila
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Mercedes Bengochea, Thomas Preat, and Bassem, A Hassan
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Biology (General) ,QH301-705.5 - Abstract
Visual learning in animals is a remarkable cognitive ability that plays a crucial role in their survival and adaptation. Therefore, the ability to learn is highly conserved among animals. Despite lacking a centralized nervous system like vertebrates, invertebrates have demonstrated remarkable learning abilities. Here, we describe a simple behavioral assay that allows the analysis of visual associative learning in individually traceable freely walking adult fruit flies. The setup is based on the simple and widely used behavioral assay to study orientation behavior in flies. A single wing-clipped fly that has been starved for 21 h is placed on a platform where two unreachable opposite visual sets are displayed. This visual learning protocol was initially developed to study the cognitive ability of fruit flies to process numerical information. Through the application of the protocol, flies are able to associate a specific visual set with an appetitive reward. This association is revealed 2 h later during the testing session where we observed a change in their preference upon learning (i.e., change in their spontaneous preference). Moreover, this protocol could potentially be used to associate any other visual object/property to the reward, expanding the opportunities of studying visual learning in freely walking fruit flies at individual level.Graphical overviewGraphical overview of conditional learning protocol. Forty-eight hours before conditioning, the wings of the flies are clipped, and individual flies are left to recover in a fresh food vial. Twenty-one hours before the conditional learning starts, flies are transferred to a starvation vial containing wet paper. The training session consists in placing a drop of sugar next to the place with the lower number of objects (numerosity) and a drop of water next to the larger numerosity. The fly is placed in the arena and left to freely walk for three minutes. Once the session is finished, the fly is placed back in their empty vial for 2 h until the testing session starts.
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- 2023
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14. 117. Comparative Analysis of Two Hemiarthroplasty Techniques for Symptomatic Distal Radial Ulnar Joint
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Nathan Sean David Hebel, BS, Elizabeth Helsper, MD, Kitty Wu, MD, Bassem El Hassan, MD, Sanjeev Kakar, MD, and Steven Moran, MD
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Surgery ,RD1-811 - Published
- 2023
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15. Autophagy in synapse formation and brain wiring
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Bassem A. Hassan and P. Robin Hiesinger
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Cell Biology ,Molecular Biology - Published
- 2023
16. The brain on time: links between development and neurodegeneration
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Khadijeh Shabani and Bassem A. Hassan
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Molecular Biology ,Developmental Biology - Abstract
Neurodegenerative diseases are characterized by the progressive loss of structure or function of neurons. In this Spotlight, we explore the idea that genetic forms of neurodegenerative disorders might be rooted in neural development. Focusing on Alzheimer's, Parkinson's and Huntington's disease, we first provide a brief overview of the pathology for these diseases. Although neurodegenerative diseases are generally thought of as late-onset diseases, we discuss recent evidence promoting the notion that they might be considered neurodevelopmental disorders. With this view in mind, we consider the suitability of animal models for studying these diseases, highlighting human-specific features of human brain development. We conclude by proposing that one such feature, human-specific regulation of neurogenic time, might be key to understanding the etiology and pathophysiology of human neurodegenerative disease.
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- 2023
17. The ribose methylation enzyme FTSJ1 has a conserved role in neuron morphology and learning performance
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Mira Brazane, Dilyana G Dimitrova, Julien Pigeon, Chiara Paolantoni, Tao Ye, Virginie Marchand, Bruno Da Silva, Elise Schaefer, Margarita T Angelova, Zornitza Stark, Martin Delatycki, Tracy Dudding-Byth, Jozef Gecz, Pierre-Yves Plaçais, Laure Teysset, Thomas Préat, Amélie Piton, Bassem A Hassan, Jean-Yves Roignant, Yuri Motorin, and Clément Carré
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Ecology ,Health, Toxicology and Mutagenesis ,Plant Science ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Humans ,Methylation ,Ribose ,Intellectual Disability/genetics ,Methyltransferases/genetics ,RNA, Transfer/genetics ,RNA, Transfer/metabolism ,Neurons/metabolism ,Nuclear Proteins/genetics - Abstract
FTSJ1 is a conserved human 2′-O-methyltransferase (Nm-MTase) that modifies several tRNAs at position 32 and the wobble position 34 in the anticodon loop. Its loss of function has been linked to X-linked intellectual disability (XLID), and more recently to cancers. However, the molecular mechanisms underlying these pathologies are currently unclear. Here, we report a novelFTSJ1pathogenic variant from an X-linked intellectual disability patient. Using blood cells derived from this patient and other affected individuals carryingFTSJ1mutations, we performed an unbiased and comprehensive RiboMethSeq analysis to map the ribose methylation on all human tRNAs and identify novel targets. In addition, we performed a transcriptome analysis in these cells and found that several genes previously associated with intellectual disability and cancers were deregulated. We also found changes in the miRNA population that suggest potential cross-regulation of some miRNAs with these key mRNA targets. Finally, we show that differentiation of FTSJ1-depleted human neural progenitor cells into neurons displays long and thin spine neurites compared with control cells. These defects are also observed inDrosophilaand are associated with long-term memory deficits. Altogether, our study adds insight into FTSJ1 pathologies in humans and flies by the identification of novel FTSJ1 targets and the defect in neuron morphology.
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- 2023
18. Transient regulation of focal adhesion via Tensin3 is required for nascent oligodendrocyte differentiation
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Hatem Hmidan, Emeric Merour, Corentine Marie, Pierre-Henri Helou, Haiyang Lu, Antoine Potel, Jean-Baptiste Hure, Adrien Clavairoly, Yi Ping Shih, Salman Goudarzi, Sebastien Dussaud, Philippe Ravassard, Sassan Hafizi, Su Hao Lo, Bassem A Hassan, and Carlos Parras
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Integrins ,Mouse ,Knockout ,Regenerative Medicine ,General Biochemistry, Genetics and Molecular Biology ,neuroscience ,Mice ,developmental biology ,immature oligodedrocyte marker ,Genetics ,Animals ,Humans ,human ,oligodendroglial survival ,Mice, Knockout ,Focal Adhesions ,General Immunology and Microbiology ,General Neuroscience ,Neurosciences ,tensin ,Cell Differentiation ,General Medicine ,Stem Cell Research ,Chromatin ,Oligodendroglia ,oligodendrocyte differentiation ,Stem Cell Research - Nonembryonic - Non-Human ,Biochemistry and Cell Biology ,Tumor Suppressor Protein p53 ,Transcription Factors - Abstract
The differentiation of oligodendroglia from oligodendrocyte precursor cells (OPCs) to complex and extensive myelinating oligodendrocytes (OLs) is a multistep process that involves largescale morphological changes with significant strain on the cytoskeleton. While key chromatin and transcriptional regulators of differentiation have been identified, their target genes responsible for the morphological changes occurring during OL myelination are still largely unknown. Here, we show that the regulator of focal adhesion, Tensin3 (Tns3), is a direct target gene of Olig2, Chd7, and Chd8, transcriptional regulators of OL differentiation. Tns3 is transiently upregulated and localized to cell processes of immature OLs, together with integrin-β1, a key mediator of survival at this transient stage. Constitutive Tns3 loss-of-function leads to reduced viability in mouse and humans, with surviving knockout mice still expressing Tns3 in oligodendroglia. Acute deletion of Tns3 in vivo, either in postnatal neural stem cells (NSCs) or in OPCs, leads to a two-fold reduction in OL numbers. We find that the transient upregulation of Tns3 is required to protect differentiating OPCs and immature OLs from cell death by preventing the upregulation of p53, a key regulator of apoptosis. Altogether, our findings reveal a specific time window during which transcriptional upregulation of Tns3 in immature OLs is required for OL differentiation likely by mediating integrin-β1 survival signaling to the actin cytoskeleton as OL undergo the large morphological changes required for their terminal differentiation.
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- 2022
19. Author response: Transient regulation of focal adhesion via Tensin3 is required for nascent oligodendrocyte differentiation
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Hatem Hmidan, Emeric Merour, Corentine Marie, Pierre-Henri Helou, Haiyang Lu, Antoine Potel, Jean-Baptiste Hure, Adrien Clavairoly, Yi Ping Shih, Salman Goudarzi, Sebastien Dussaud, Philippe Ravassard, Sassan Hafizi, Su Hao Lo, Bassem A Hassan, and Carlos Parras
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- 2022
20. Author Reply to Peer Reviews of Transient regulation of focal adhesion via Tensin3 is required for nascent oligodendrocyte differentiation
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Carlos Parras, Bassem A. Hassan, Su Hao Lo, Sassan Hafizi, Philippe Ravassard, Sebastien Dussaud, Salman Goudarzi, Yi Ping Shih, Adrien Clavairoly, Jean-Baptiste Hure, Antoine Potel, Haiyang Lu, Pierre-Henri Helou, Corentine Marie, Hatem Hmidan, and Emeric Merour
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- 2022
21. A critical developmental interval of coupling axon branching to synaptic degradation during neural circuit formation
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Suchetana B. Dutta, Gerit Arne Linneweber, Maheva Andriatsilavo, Peter Robin Hiesinger, and Bassem A Hassan
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History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Abstract
The emergence of neuronal wiring specificity requires stabilization of dynamic axonal branches at sites of selective synapse formation. Models that explain how axonal branching is coupled to synaptogenesis postulate molecular regulators acting in a spatiotemporally restricted fashion. We report that Epidermal Growth Factor Receptor (EGFR) activity is required in presynaptic axonal branches during two distinct temporal intervals to regulate circuit wiring in the developing Drosophila visual system. EGFR is required early to regulate primary axonal branching and independently again later to prevent autophagic degradation of the synaptic active zone protein Bruchpilot (Brp). The protection of synaptic material during this later interval of wiring ensures the stabilization of terminal branches, circuit connectivity and appropriate visual behavior. Phenotypes of EGFR inactivation were rescued by increasing Brp levels or downregulating autophagic genes. We identify a temporally restricted molecular mechanism required for coupling axonal branching and synaptic stabilization that contributes to the emergence of neuronal wiring specificity.
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- 2022
22. EGFR-dependent suppression of synaptic autophagy is required for neuronal circuit development
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Suchetana B. Dutta, Gerit Arne Linneweber, Maheva Andriatsilavo, Peter Robin Hiesinger, and Bassem A. Hassan
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General Agricultural and Biological Sciences ,General Biochemistry, Genetics and Molecular Biology - Published
- 2023
23. Numerical discrimination in Drosophila melanogaster
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Mercedes Bengochea, Jacobo D. Sitt, Thomas Preat, Veronique Izard, Laurent Cohen, and Bassem A. Hassan
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Sensitivity to numbers is a crucial and evolutionarily conserved cognitive ability. The lack of experimental models amenable to systematic genetic and neural manipulation has precluded discovering circuits required for numerical cognition. Here, we demonstrate that in a two-choice task Drosophila fruit flies spontaneously prefer sets containing more objects. This preference is determined by the ratio between the two numerical quantities tested, a characteristic signature of numerical cognition across species. Individual flies maintained their numerical choice over consecutive days. Using a numerical visual conditioning paradigm, we found that flies are capable of associating sucrose with numerical quantities and can be trained to reverse their spontaneous preference for large quantities. Finally, we show that silencing LC11 neurons reduces the preference for more objects, thus identifying a neuronal substrate for numerical cognition in invertebrates. This discovery paves the way for the systematic analysis of the behavioral and neural mechanisms underlying sensitivity to numerosity.
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- 2022
24. Arthroscopic pectoralis minor tenotomy
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L. Pearce McCarty and Bassem El Hassan
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- 2022
25. Contributors
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Abed Abdelaziz, Geoffrey D. Abrams, Christopher R. Adams, Zahab S. Ahsan, Doruk Akgün, Michael J. Alaia, Nedal Al-Khatib, Answorth A. Allen, David W. Altchek, Annunziato Amendola, Brittany M. Ammerman, Luca Andriolo, Peter Angele, Adam Anz, Elizabeth A. Arendt, Justin W. Arner, Neal S. Elattrache, Frederick M. Azar, Bernard R. Bach, Joanne Page Elston Baird, Champ L. Baker, Christopher P. Bankhead, Ryan H. Barnes, Lachlan Batty, Asheesh Bedi, Knut Beitzel, John W. Belk, Neilen A. Benvegnu, Andrew Bernhardson, David L. Bernholt, Daniel P. Berthold, Blake M. Bodendorfer, Angelo Boffa, Pascal Boileau, Kyle Borque, Craig R. Bottoni, James P. Bradley, Tyler J. Brolin, Matthew L. Brown, Robert Browning, William D. Bugbee, Gaetano Lo Bue, Joseph P. Burns, Charles A. Bush-Joseph, Jacob G. Calcei, Jourdan M. Cancienne, Connor K. Cannizzaro, James B. Carr, Thomas R. Carter, Simone Cerciello, Jorge Chahla, Peter N. Chalmers, Neal C. Chen, Timothy T. Cheng, Mark S. Cohen, Brian J. Cole, Nolan B. Condron, Corey S. Cook, Joe D. Cooper, R. Alexander Creighton, Navya Dandu, Richard M. Danilkowicz, Victor Danzinger, Robert S. Dean, Thomas DeBerardino, Laura DeGirolamo, David DeJour, Connor M. Delman, Ian J. Dempsey, Patrick J. Denard, Eric J. Dennis, Aman Dhawan, Aad A.M. Dhollander, Connor C. Diaz, Jonathan F. Dickens, David Diduch, Alessandro Di Martino, Joshua S. Dines, Brenton W. Douglass, Justin Drager, Alex G. Dukas, Corey R. Dwyer, Nicholas J. Ebert, Bassem El Hassan, Johnny El Rayes, Bryant P. Elrick, Brandon J. Erickson, Aghogho Evuarherhe, Gregory C. Fanelli, Jack Farr, John J. Fernandez, Larry D. Field, Giuseppe Filardo, Julia Fink, David C. Flanigan, Enrico M. Forlenza, Brian Forsythe, Thomas Fradin, Rachel M. Frank, Michael T. Freehill, Heather Freeman, Lisa G.M. Friedman, Steven DeFroda, Freddie H. Fu, John P. Fulkerson, Ian Gao, Grant E. Garrigues, Pablo E. Gelber, Alan Getgood, Ron Gilat, Scott D. Gillogly, Daniel B. Goldberg, Andreas H. Gomoll, Benjamin R Graves, Tinker Gray, Nathan L. Grimm, Florian Grubhofer, Jordan A. Gruskay, Ibrahim M. Haidar, James Hammond, Fucai Han, Payton Harris, Robert U. Hartzler, Carolyn M. Hettrich, Justin E. Hill, Takashi Hoshino, Benjamin W. Hoyt, Hailey P. Huddleston, Jonathan D. Hughes, Anthony J. Ignozzi, Mary Lloyd Ireland, Eiji Itoi, Evan W. James, Andrew E. Jimenez, Christopher C. Kaeding, Ajay C. Kanakamedala, James S. Kercher, Benjamin S. Kester, W. Ben Kibler, Derrick M. Knapik, Thomas P. Knapp, Baris Kocaoglu, Marc Korn, Avinaash Korrapati, John E. Kuhn, Laurent Lafosse, Thibault Lafosse, Joseph D. Lamplot, Robert F. LaPrade, Lior Laver, Arash Lavian, Ophelie Z. Lavoie-Gagne, Lance E. LeClere, Kenneth M. Lin, Adam Lindsay, Laughter Lisenda, Robert Litchfield, Bhargavi Maheshwer, Eric C. Makhni, Nathan Mall, Richard A. Marder, Fabrizio Margheritini, Robert G. Marx, David Matson, Augustus D. Mazzocca, Eric C. McCarty, L. Pearce McCarty, Ashley Mehl, Kaare S. Midtgaard, Mark D. Miller, Peter J. Millett, Raffy Mirzayan, Gilbert Moatshe, Jill Monson, Christian Moody, Philipp Moroder, Andres R. Muniz Martinez, Stefano Muzzi, Emily Naclerio, Levy Nathan, Philipp Niemeyer, Cédric Ngbilo, Gregory P. Nicholson, Philip-C. Nolte, Ali S. Noorzad, Gordon Nuber, Michael J. O’Brien, Robert S. O’Connell, Evan A. O’Donnell, Kieran O’Shea, James L. Pace, Michael J. Pagnani, Kevin C. Parvaresh, Jhillika Patel, Liam A. Peebles, Evan M. Polce, Rodrigo Sandoval Pooley, CAPT Matthew T. Provencher, Ryan J. Quigley, Courtney Quinn, M. Brett Raynor, David Ring, Avi S. Robinson, Scott A. Rodeo, William G. Rodkey, Anthony A. Romeo, Joseph J. Ruzbarsky, Orlando D. Sabbag, Marc R. Safran, Michael J. Salata, Ian Savage-Elliott, Felix H. Savoie, Donald J Scholten, Aaron Sciascia, K. Donald Shelbourne, Seth L. Sherman, Monica M. Shoji, Adam M. Smith, Matthew V. Smith, Patrick A. Smith, Bertrand Sonnery-Cottet, Yosef Sourugeon, Eric J. Strauss, Caroline Struijk, Geoffrey S. Van Thiel, John M. Tokish, Marc Tompkins, Joseph S. Tramer, Nicholas Trasolini, Anna Tross, Colin L. Uyeki, Evan E. Vellios, Angelina M. Vera, Peter C.M. Verdonk, René Verdonk, Dirk W. Verheul, Nikhil N. Verma, Thais Dutra Vieira, Gustavo Vinagre, Kyle R. Wagner, Jordan D. Walters, Jon J.P. Warner, Russell F. Warren, Brian R. Waterman, Karl Wieser, Brady T. Williams, Andy Williams, Matthew T. Winterton, Kelsey Wise, Stephanie Wong, Ivan Wong, Elisabeth Wörner, Joshua Wright-Chisem, Robert W. Wysocki, Nobuyuki Yamamoto, Adam B. Yanke, Yaniv Yonai, Anthony J. Zacharias, and Alexander Ziedas
- Published
- 2022
26. A neurodevelopmental origin of behavioral individuality in the Drosophila visual system
- Author
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Andrew Straw, Peter Robin Hiesinger, Bassem A. Hassan, Suchetana Bias Dutta, Liz Hellbruegge, Maheva Andriatsilavo, Guangda Liu, Gerit A. Linneweber, Mercedes Bengochea, Mathias F. Wernet, and Radoslaw K. Ejsmont
- Subjects
0303 health sciences ,Multidisciplinary ,Brain development ,biology ,media_common.quotation_subject ,Stochastic variation ,Object (grammar) ,biology.organism_classification ,Behavioral variation ,03 medical and health sciences ,0302 clinical medicine ,Variation (linguistics) ,Contrast (vision) ,Drosophila melanogaster ,Drosophila ,Neuroscience ,030217 neurology & neurosurgery ,030304 developmental biology ,media_common - Abstract
Diversity from development When given a line to follow, some fruit flies do so carefully and others weave. Linneweber et al. now show that these behaviors are stable for an individual but diverse in an isogenic population. Key to generating individual diversity in the population is the inherent chaos of normal development. A set of neurons in the visual system is wired up in a variable manner, resulting in brain circuit asymmetry unique to each fly that guides its line-walking behavior. With more asymmetry in its brain circuit, a fly is better able to orient to the line. Science , this issue p. 1112
- Published
- 2020
27. Slit neuronal secretion coordinates optic lobe morphogenesis in Drosophila
- Author
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Pablo Guzmán-Palma, Carlos Oliva, Lorena Caipo, Esteban G. Contreras, Jorge M. Campusano, Tomás Palominos, Jimena Sierralta, Nicolás Fuenzalida-Uribe, Bassem A. Hassan, and M. Constanza González-Ramírez
- Subjects
Nervous system ,Neuropil ,genetic structures ,Morphogenesis ,Nerve Tissue Proteins ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Genes, Reporter ,Netrin ,medicine ,Animals ,Drosophila Proteins ,Transgenes ,Receptors, Immunologic ,Molecular Biology ,Genetic Association Studies ,030304 developmental biology ,Neurons ,0303 health sciences ,Optic Lobe, Nonmammalian ,Pupa ,Cell migration ,Cell Biology ,Slit ,eye diseases ,Transmembrane protein ,Neural stem cell ,Axon Guidance ,Cell biology ,Drosophila melanogaster ,Enhancer Elements, Genetic ,Phenotype ,medicine.anatomical_structure ,nervous system ,Organ Specificity ,Gene Knockdown Techniques ,Larva ,Mutation ,RNA Interference ,Axon guidance ,sense organs ,Neuroglia ,Photic Stimulation ,030217 neurology & neurosurgery ,Transcription Factors ,Developmental Biology - Abstract
The complexity of the nervous system requires the coordination of multiple cellular processes during development. Among them, we find boundary formation, axon guidance, cell migration and cell segregation. Understanding how different cell populations such as glial cells, developing neurons and neural stem cells contribute to the formation of boundaries and morphogenesis in the nervous system is a critical question in neurobiology. Slit is an evolutionary conserved protein essential for the development of the nervous system. For signaling, Slit has to bind to its cognate receptor Robo, a single-pass transmembrane protein. Although the Slit/Robo signaling pathway is well known for its involvement in axon guidance, it has also been associated to boundary formation in the Drosophila visual system. In the optic lobe, Slit is expressed in glial cells, positioned at the boundaries between developing neuropils, and in neurons of the medulla ganglia. Although it has been assumed that glial cells provide Slit to the system, the contribution of the neuronal expression has not been tested. Here, we show that, contrary to what was previously thought, Slit protein provided by medulla neurons is also required for boundary formation and morphogenesis of the optic lobe. Furthermore, tissue specific rescue using modified versions of Slit demonstrates that this protein acts at long range and does not require processing by extracellular proteases. Our data shed new light on our understanding of the cellular mechanisms involved in Slit function in the fly visual system morphogenesis.
- Published
- 2020
28. The amyloid precursor protein is a conserved Wnt receptor
- Author
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Alessia Soldano, Bart De Strooper, Bassem A. Hassan, Lee G. Fradkin, Lydie Boussicault, Heather C. Rice, Marie-Claude Potier, Iveta M. Petrova, Annelies Claeys, Tengyuan Liu, Maya Nicolas, Tingting Zhang, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Center for Human Genetics, University of Leuven School of Medicine, SCHOOL of MEDICINE [Louvain], Université Catholique de Louvain = Catholic University of Louvain (UCL)-Université Catholique de Louvain = Catholic University of Louvain (UCL), VIB Center for the Biology of Disease [Louvain, Belgique] (VIB-CBD), Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Gestionnaire, HAL Sorbonne Université 5, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Life Sciences & Biomedicine - Other Topics ,DIMERIZATION ,brain development ,amyloid precursor protein ,neuroscience ,Amyloid beta-Protein Precursor ,Mice ,0302 clinical medicine ,DOMAIN ,BINDING ,cell biology ,Receptors ,D. melanogaster ,Drosophila ,alzheimer's disease ,mouse ,wnt ,Amino Acid Sequence ,Animals ,Brain ,Cells, Cultured ,Cloning, Molecular ,Drosophila Proteins ,Drosophila melanogaster ,Gene Deletion ,Gene Expression Regulation ,Humans ,Membrane Proteins ,Mushroom Bodies ,Nerve Tissue Proteins ,Neurons ,Protein Transport ,Receptors, Wnt ,Signal Transduction ,Amyloid precursor protein ,Biology (General) ,Receptor ,0303 health sciences ,Cultured ,biology ,Chemistry ,General Neuroscience ,Wnt signaling pathway ,General Medicine ,Phenotype ,Transmembrane protein ,Cell biology ,ALZHEIMERS-DISEASE ,WNT5A ,Medicine ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Life Sciences & Biomedicine ,POLARITY ,Research Article ,EXPRESSION ,QH301-705.5 ,Cells ,Science ,General Biochemistry, Genetics and Molecular Biology ,Wnt ,03 medical and health sciences ,mental disorders ,Extracellular ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Biology ,030304 developmental biology ,Science & Technology ,General Immunology and Microbiology ,Molecular ,Cell Biology ,ESTABLISHMENT ,biology.protein ,APP ,030217 neurology & neurosurgery ,WNT3A ,Cloning ,Neuroscience - Abstract
The Amyloid Precursor Protein (APP) and its homologues are transmembrane proteins required for various aspects of neuronal development and activity, whose molecular function is unknown. Specifically, it is unclear whether APP acts as a receptor, and if so what its ligand(s) may be. We show that APP binds the Wnt ligands Wnt3a and Wnt5a and that this binding regulates APP protein levels. Wnt3a binding promotes full-length APP (flAPP) recycling and stability. In contrast, Wnt5a promotes APP targeting to lysosomal compartments and reduces flAPP levels. A conserved Cysteine-Rich Domain (CRD) in the extracellular portion of APP is required for Wnt binding, and deletion of the CRD abrogates the effects of Wnts on flAPP levels and trafficking. Finally, loss of APP results in increased axonal and reduced dendritic growth of mouse embryonic primary cortical neurons. This phenotype can be cell-autonomously rescued by full length, but not CRD-deleted, APP and regulated by Wnt ligands in a CRD-dependent manner. ispartof: ELIFE vol:10 ispartof: location:England status: published
- Published
- 2021
29. Author response: The amyloid precursor protein is a conserved Wnt receptor
- Author
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Bart De Strooper, Lee G. Fradkin, Iveta M. Petrova, Alessia Soldano, Marie-Claude Potier, Annelies Claeys, Maya Nicolas, Bassem A. Hassan, Lydie Boussicault, Tengyuan Liu, Heather C. Rice, and Tingting Zhang
- Subjects
biology ,Chemistry ,Amyloid precursor protein ,biology.protein ,Wnt signaling pathway ,Receptor ,Cell biology - Published
- 2021
30. Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum
- Author
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Andi H. Hansen, Natalia Mora, Natalia Danda, Justine Guegan, Luca Tiberi, Simon Hippenmeyer, Mathilde Bertrand, Marica Anderle, Tingting Zhang, Carmen Streicher, Tengyuan Liu, Ximena Contreras, Bassem A. Hassan, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institute of Science and Technology [Austria] (IST Austria), University of Trento [Trento], HAL-SU, Gestionnaire, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Institute of Science and Technology [Klosterneuburg, Austria] (IST Austria)
- Subjects
0301 basic medicine ,DOUBLE MARKERS ,EXPRESSION ,Cerebellum ,GLIOGENESIS ,MOSAIC ANALYSIS ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Notch signaling pathway ,Biology ,Cell fate determination ,Inhibitory postsynaptic potential ,General Biochemistry, Genetics and Molecular Biology ,NEUROGENESIS ,03 medical and health sciences ,0302 clinical medicine ,[SDV.BDD] Life Sciences [q-bio]/Development Biology ,medicine ,Humans ,human cerebellar organoids ,SPECIFICATION ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,Notch signaling ,030304 developmental biology ,Progenitor ,neural stem cells ,Neurons ,0303 health sciences ,Science & Technology ,Receptors, Notch ,Neurogenesis ,[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Cell Differentiation ,neuronal diversity ,Cell Biology ,STEM ,Embryonic stem cell ,mouse cerebellum ,Neural stem cell ,030104 developmental biology ,medicine.anatomical_structure ,DIFFERENTIATION ,MEDULLOBLASTOMA ,Excitatory postsynaptic potential ,Neuroscience ,Life Sciences & Biomedicine ,INTEGRATION ,030217 neurology & neurosurgery - Abstract
SUMMARYBrain neurons arise from relatively few progenitors capable of giving rise to an enormous diversity of neuronal types. Nonetheless, a cardinal feature of mammalian brain neurogenesis in both the cortex and the cerebellum is that excitatory neurons and inhibitory neurons derive from separate, spatially segregated, progenitors. Whether bi-potential progenitors with an intrinsic capacity to generate both excitatory and inhibitory lineages exist and how such a fate decision may be regulated is unknown. Using cerebellar development as a model, we discover that individual embryonic cerebellar progenitors give rise to both inhibitory and excitatory lineages. We find that gradations of Notch activity levels determine the fates of the progenitors and their daughters. Daughters with the highest levels of Notch activity retain the progenitor fate. Daughters with intermediate levels of Notch activity become fate restricted to generate inhibitory neurons, while daughters with very low levels of Notch signaling adopt the excitatory fate. Therefore, Notch mediated binary cell fate choice is a mechanism for regulating the ratio of excitatory to inhibitory neurons from common progenitors.Graphical summary
- Published
- 2021
31. Brain connectivity inversely scales with developmental temperature in Drosophila
- Author
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Ferdi Ridvan Kiral, Suchetana B. Dutta, Gerit Arne Linneweber, Selina Hilgert, Caroline Poppa, Carsten Duch, Max von Kleist, Bassem A. Hassan, P. Robin Hiesinger, Freie Universität Berlin, Institute of Developmental Biology and Neurobiology, University of Mainz, Robert Koch Institute [Berlin] (RKI), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Gestionnaire, Hal Sorbonne Université
- Subjects
synaptic specificity ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Neurogenesis ,brain development ,neuronal connectivity ,General Biochemistry, Genetics and Molecular Biology ,brain wiring ,filopodia ,branching ,Animals ,Drosophila Proteins ,developmental temperature ,Brain connectivity ,Neurons ,behavior ,variability ,[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Temperature ,Brain ,500 Naturwissenschaften und Mathematik::570 Biowissenschaften ,Biologie::570 Biowissenschaften ,Biologie ,Adaptation, Physiological ,Axons ,Synapses ,Drosophila ,Photoreceptor Cells, Invertebrate - Abstract
International audience; Variability of synapse numbers and partners despite identical genes reveals the limits of genetic determinism. Here, we use developmental temperature as a non-genetic perturbation to study variability of brain wiring and behavior in Drosophila. Unexpectedly, slower development at lower temperatures increases axo-dendritic branching, synapse numbers, and non-canonical synaptic partnerships of various neurons, while maintaining robust ratios of canonical synapses. Using R7 photoreceptors as a model, we show that changing the relative availability of synaptic partners using a DIPγ mutant that ablates R7's preferred partner leads to temperature-dependent recruitment of non-canonical partners to reach normal synapse numbers. Hence, R7 synaptic specificity is not absolute but based on the relative availability of postsynaptic partners and presynaptic control of synapse numbers. Behaviorally, movement precision is temperature robust, while movement activity is optimized for the developmentally encountered temperature. These findings suggest genetically encoded relative and scalable synapse formation to develop functional, but not identical, brains and behaviors.
- Published
- 2021
32. Variable brain wiring through scalable and relative synapse formation inDrosophila
- Author
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Ferdi Ridvan Kiral, Bassem A. Hassan, Dutta Sb, Poppa C, Peter Robin Hiesinger, Gerit A. Linneweber, and von Kleist M
- Subjects
Synapse ,biology ,Scalability ,Synapse formation ,Movement activity ,biology.organism_classification ,Drosophila ,Neuroscience - Abstract
Variability of synapse numbers and partners despite identical genes reveals limits of genetic determinism. Non-genetic perturbation of brain wiring can therefore reveal to what extent synapse formation is precise and absolute, or promiscuous and relative. Here, we show the role of relative partner availability for synapse formation in the fly brain through perturbation of developmental temperature. Unexpectedly, slower development at lower temperatures substantially increases axo-dendritic branching, synapse numbers and non-canonical synaptic partnerships of various neurons, while maintaining robust ratios of canonical synapses. Using R7 photoreceptors as a model, we further show that scalability of synapse numbers and ratios is preserved when relative availability of synaptic partners is changed in a DIPγ mutant that ablates R7’s preferred synaptic partner. Behaviorally, movement activity scales inversely with synapse numbers, while movement precision and relative connectivity are congruently robust. Hence, the fly genome encodes scalable relative connectivity to develop functional, but not identical, brains.One-Sentence SummaryNon-identical connectivity and behavior result from temperature-dependent synaptic partner availability inDrosophila.
- Published
- 2021
33. Decision letter: A developmental framework linking neurogenesis and circuit formation in the Drosophila CNS
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Isabel Holguera and Bassem A. Hassan
- Subjects
biology ,Neurogenesis ,Drosophila (subgenus) ,biology.organism_classification ,Neuroscience - Published
- 2021
34. The temporal balance between self-renewal and differentiation of human neural stem cells requires the Amyloid Precursor Protein
- Author
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Ridha Limame, Khadijeh Shabani, Tengyuan Liu, Carlos Parras, Delphine Bohl, Marwan Benaissa Touil Zariouh, Natasha Danda, Julien Pigeon, Bassem A. Hassan, Elise Liu, Jun Komatsu, and Azadeh Saffarian
- Subjects
Neocortex ,biology ,Neurogenesis ,Wnt signaling pathway ,Neural stem cell ,Cell biology ,AP-1 transcription factor ,medicine.anatomical_structure ,nervous system ,Amyloid precursor protein ,biology.protein ,medicine ,Transcription factor ,Progenitor - Abstract
The approximately 16 billion neurons of the human neocortex are derived from a relatively limited number of developmental neural stem cells (NSCs). During embryogenesis, human cortical NSCs initially generate neurons at a particularly slow rate while preserving their progenitor state for a relatively long time. How this balance between the progenitor state and neurogenic state is regulated, and whether it contributes to species-specific brain patterning, is poorly understood. Here we show that the characteristic potential of human NSCs to remain in a progenitor state as they generate neurons for a prolonged amount of time requires the Amyloid Precursor Protein (APP). In contrast, APP is dispensable in mouse NSCs, which undergo neurogenesis at a much faster rate. Mechanistically, loss of APP cell-autonomously accelerates neurogenesis through activation of the AP1 transcription factor and repression of WNT signaling. We propose that the fine balance between self-renewal and differentiation is homeostatically regulated by APP, which may contribute to human-specific temporal patterns of neurogenesis.
- Published
- 2021
35. The ribose methylation enzyme FTSJ1 has a conserved role in neuron morphology and learning performance
- Author
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Bassem A. Hassan, Pierre-Yves Plaçais, Tao Ye, Thomas Preat, Jozef Gecz, Jean-Yves Roignant, Tracy Dudding-Byth, Julien Pigeon, Clément Carré, Dilyana G. Dimitrova, Zornitza Stark, Yuri Motorin, Laure Teysset, Martin B. Delatycki, Bruno Da Silva, Mira Brazane, Virginie Marchand, Margarita T Angelova, Chiara Paolantoni, Elise Schaefer, and Amélie Piton
- Subjects
Transcriptome ,education.field_of_study ,Neurite ,Transfer RNA ,microRNA ,Population ,Methylation ,Biology ,education ,Gene ,Loss function ,Cell biology - Abstract
FTSJ1 is a conserved human 2’-O-methyltransferase (Nm-MTase) that modifies several transfer RNAs (tRNAs) at position 32 and the wobble position 34 in the AntiCodon Loop (ACL). Its loss of function has been linked to Non-Syndromic X-Linked Intellectual Disability (NSXLID), and more recently to cancers. However, the molecular mechanisms underlying these pathologies are currently unclear. Here we report a novelFTSJ1pathogenic variant from a NSXLID patient. Using blood cells derived from this patient and other affected individuals carryingFTSJ1mutations, we performed an unbiased and comprehensive RiboMethSeq analysis to map the ribose methylation (Nm) on all human tRNAs and identify novel targets. In addition, we performed a transcriptome analysis in these cells and found that several genes previously associated with intellectual disability and cancers were deregulated. We also found changes in the miRNA population that suggest potential cross-regulation of some miRNAs with these key mRNA targets. Finally, we show that differentiation of FTSJ1-depleted human neuronal progenitor cells (NPC) into neurons displays long and thin spine neurites compared to control cells. These defects are also observed inDrosophilaand are associated with long term memory deficit in this organism. Altogether, our study adds insight into FTSJ1 pathologies in human and flies by the identification of novel FTSJ1 targets and the defect in neuron morphology.
- Published
- 2021
36. The Amyloid Precursor Protein is a conserved Wnt receptor
- Author
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Maya Nicolas, Lee G. Fradkin, Bart De Strooper, Alessia Soldano, Tingting Zhang, Iveta M. Petrova, Tengyuan Liu, Annelies Claeys, Heather C. Rice, and Bassem A. Hassan
- Subjects
WNT5A ,biology ,Chemistry ,mental disorders ,Wnt signaling pathway ,Amyloid precursor protein ,biology.protein ,Extracellular ,Receptor ,Phenotype ,Transmembrane protein ,WNT3A ,Cell biology - Abstract
SUMMARYThe Amyloid Precursor Protein (APP) and its homologues are transmembrane proteins required for various aspects of neuronal development and activity, whose molecular function is unknown. Specifically, it is unclear whether APP acts as a receptor, and if so what its ligand(s) may be. We show that APP binds the Wnt ligands Wnt3a and Wnt5a and that this binding regulates APP protein levels. Wnt3a binding promotes full length APP (flAPP) recycling and stability. In contrast, Wnt5a promotes APP targeting to lysosomal compartments and reduces flAPP levels. A conserved Cysteine Rich Domain (CRD) in the extracellular portion of APP is required for Wnt binding, and deletion of the CRD abrogates the effects of Wnts on flAPP levels and trafficking. Finally, loss of APP results in increased axonal and reduced dendritic growth of mouse embryonic primary cortical neurons. This phenotype can be cell-autonomously rescued by full length, but not CRD-deleted, APP.
- Published
- 2021
37. The Balance Between Self-Renewal and Differentiation of Human Neural Stem Cells Requires the Amyloid Precursor Protein
- Author
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Natasha Danda, Tengyuan Liu, Carlos Parras, Ridha Limame, Bassem A. Hassan, Marwan Benaissa Touil Zariouh, Azadeh Saffarian, Khadijeh Shabani, Jun Kamatsu, Elise Liu, Delphine Bohl, and Julien Pigeon
- Subjects
History ,Neocortex ,Polymers and Plastics ,Neurogenesis ,Wnt signaling pathway ,Biology ,Industrial and Manufacturing Engineering ,Neural stem cell ,Cell biology ,medicine.anatomical_structure ,nervous system ,medicine ,Amyloid precursor protein ,biology.protein ,Business and International Management ,Transcription factor ,Psychological repression ,Progenitor - Abstract
The approximately 16 billion neurons of the human neocortex are derived from a relatively limited number of developmental neural stem cells (NSCs). During embryogenesis, human cortical NSCs initially generate neurons at a particularly slow rate while preserving their progenitor state for a relatively long time. How this balance between the progenitor state and neurogenic state is regulated, and whether it contributes to species-specific brain patterning, is poorly understood. Here we show that the characteristic potential of human NSCs to remain in a progenitor state as they generate neurons for a prolonged amount of time requires the Amyloid Precursor Protein (APP). In contrast, APP is dispensable in mouse NSCs, which undergo neurogenesis at a much faster rate. Mechanistically, loss of APP cell-autonomously accelerates neurogenesis through activation of the AP-1 transcription factor and repression of WNT signaling. We propose that the fine balance between self-renewal and differentiation is homeostatically regulated by APP, which may contribute to human-specific temporal patterns of neurogenesis.
- Published
- 2021
38. Notch1 switches progenitor competence in inducing medulloblastoma
- Author
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Matteo Gianesello, Tingting Zhang, Giuseppe Aiello, Francesca Gianno, Luca Tiberi, Francesco Antonica, Bassem A. Hassan, Felice Giangaspero, Konstantin Okonechnikov, Claudio Ballabio, Chiara Lago, Stefan M. Pfister, Marica Anderle, University of Trento [Trento], Hopp Children's Cancer Center Heidelberg [Heidelber, Germany] (KITZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-Heidelberg University Hospital [Heidelberg], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Istituto Neurologico Mediterraneo (NEUROMED I.R.C.C.S.), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]-Università degli studi di Napoli Federico II, Heidelberg University Hospital [Heidelberg], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA)-University of Naples Federico II = Università degli studi di Napoli Federico II, and HAL-SU, Gestionnaire
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Poor prognosis ,Cell of origin ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biology ,03 medical and health sciences ,[SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics ,0302 clinical medicine ,Developmental Neuroscience ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,SOX2 ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,medicine ,neoplasms ,Research Articles ,Cancer ,030304 developmental biology ,Progenitor ,Medulloblastoma ,0303 health sciences ,Mouse Cerebellum ,[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics ,Multidisciplinary ,[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,SciAdv r-articles ,medicine.disease ,Molecular biology ,nervous system diseases ,3. Good health ,stomatognathic diseases ,ASCL1 ,030220 oncology & carcinogenesis ,embryonic structures ,cardiovascular system ,Cancer research ,[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Pathway activity ,Research Article ,Proto-oncogene tyrosine-protein kinase Src - Abstract
Notch1 pathway activation is required for group 3 medulloblastoma initiation., The identity of the cell of origin is a key determinant of cancer subtype, progression, and prognosis. Group 3 medulloblastoma (MB) is a malignant childhood brain cancer with poor prognosis and few candidates as putative cell of origin. We overexpressed the group 3 MB genetic drivers MYC and Gfi1 in different candidate cells of origin in the postnatal mouse cerebellum. We found that S100b+ cells are competent to initiate group 3 MB, and we observed that S100b+ cells have higher levels of Notch1 pathway activity compared to Math1+ cells. We found that additional activation of Notch1 in Math1+ and Sox2+ cells was sufficient to induce group 3 MB upon MYC/Gfi1 expression. Together, our data suggest that the Notch1 pathway plays a critical role in group 3 MB initiation.
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- 2021
39. Quand le développement du cerveau façonne l’individualité comportementale
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Maheva Andriatsilavo, Bassem A. Hassan, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Sciences, EDP, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
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[SDV] Life Sciences [q-bio] ,0303 health sciences ,03 medical and health sciences ,0302 clinical medicine ,[SDV]Life Sciences [q-bio] ,General Medicine ,Biology ,030217 neurology & neurosurgery ,General Biochemistry, Genetics and Molecular Biology ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology - Abstract
International audience; No abstract available
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- 2020
40. Generation of neuronal diversity from common progenitors via Notch signaling in the cerebellum
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Andi H. Hansen, Tingting Zhang, Ximena Contreras, Mathilde Bertrand, Tengyuan Liu, Justine Guegan, Natalia Mora, Luca Tiberi, Bassem A. Hassan, Marica Anderle, Simon Hippenmeyer, and Carmen Streicher
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Cerebellum ,050208 finance ,05 social sciences ,Notch signaling pathway ,Cell fate determination ,Biology ,Inhibitory postsynaptic potential ,Embryonic stem cell ,Neural stem cell ,medicine.anatomical_structure ,nervous system ,0502 economics and business ,medicine ,050207 economics ,Progenitor cell ,Neuroscience ,Progenitor - Abstract
Summary The bewildering diversity of brain neurons arises from relatively few pluripotent progenitors through poorly understood mechanisms. The cerebellum is an attractive model to investigate mechanisms of neuronal diversification because the different subtypes of excitatory and inhibitory neurons are well described 1,2 . The cerebellum is a hub for control of motor function and contributes to a number of higher brain functions such as reward-related cognitive processes 3 . Deficits in cerebellar development lead to severe neurological disorders such as cerebellar ataxias 4 and medulloblastomas 5 , a heterogeneous and severe groups of childhood brain tumors, thus underlying the importance of understanding the cellular and molecular control of cerebellar development. In contrast to text book models, we report that excitatory and inhibitory cerebellar neurons derive from the same pluripotent embryonic cerebellar stem cells (eCSC). We find that the excitatory versus inhibitory fate decision of a progenitor is regulated by Notch signaling, whereby the cell with lower Notch activity adopts the excitatory fate, while the cell with higher Notch activity adopts the inhibitory fate. Thus, Notch-mediated binary cell fate choice is a conserved strategy for generating neuronal diversity from common progenitors that is deployed at different developmental time points in a context specific manner.
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- 2020
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41. The Drosophila Amyloid Precursor Protein homologue mediates neuronal survival and neuro-glial interactions
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Amr Hasan, Dominique Langui, Maral Maral, Suchetana Bias Dutta, Irini A. Kessissoglou, Peter Robin Hiesinger, Bassem A. Hassan, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Freie Universität Berlin, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Gestionnaire, Hal Sorbonne Université
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0301 basic medicine ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Apoptosis ,Biochemistry ,Amyloid beta-Protein Precursor ,0302 clinical medicine ,Animal Cells ,Loss of Function Mutation ,Medicine and Health Sciences ,Amyloid precursor protein ,Drosophila Proteins ,Brain Damage ,Biology (General) ,Neurons ,Neuronal Death ,0303 health sciences ,Cell Death ,biology ,General Neuroscience ,Drosophila Melanogaster ,Wnt signaling pathway ,Eukaryota ,Brain ,Animal Models ,Transmembrane protein ,3. Good health ,Cell biology ,[SDV] Life Sciences [q-bio] ,Insects ,Experimental Organism Systems ,Neurology ,Cell Processes ,Drosophila ,Cellular Types ,Cellular Structures and Organelles ,Axotomy ,Drosophila melanogaster ,General Agricultural and Biological Sciences ,Neuroglia ,Research Article ,Signal Transduction ,Programmed cell death ,Arthropoda ,QH301-705.5 ,Cell Survival ,Endosome ,Nerve Tissue Proteins ,Endosomes ,Research and Analysis Methods ,Green Fluorescent Protein ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Model Organisms ,Alzheimer Disease ,medicine ,Animals ,Vesicles ,Loss function ,030304 developmental biology ,General Immunology and Microbiology ,fungi ,Organisms ,Biology and Life Sciences ,Proteins ,Membrane Proteins ,Cell Biology ,biology.organism_classification ,Invertebrates ,Luminescent Proteins ,030104 developmental biology ,Cellular Neuroscience ,Animal Studies ,biology.protein ,Carrier Proteins ,Zoology ,Entomology ,030217 neurology & neurosurgery ,Neuroscience - Abstract
The amyloid precursor protein (APP) is a structurally and functionally conserved transmembrane protein whose physiological role in adult brain function and health is still unclear. Because mutations in APP cause familial Alzheimer’s disease (fAD), most research focuses on this aspect of APP biology. We investigated the physiological function of APP in the adult brain using the fruit fly Drosophila melanogaster, which harbors a single APP homologue called APP Like (APPL). Previous studies have provided evidence for the implication of APPL in neuronal wiring and axonal growth through the Wnt signaling pathway during development. However, like APP, APPL continues to be expressed in all neurons of the adult brain where its functions and their molecular and cellular underpinnings are unknown. We report that APPL loss of function (LOF) results in the dysregulation of endolysosomal function in neurons, with a notable enlargement of early endosomal compartments followed by neuronal cell death and the accumulation of dead neurons in the brain during a critical period at a young age. These defects can be rescued by reduction in the levels of the early endosomal regulator Rab5, indicating a causal role of endosomal function for cell death. Finally, we show that the secreted extracellular domain of APPL interacts with glia and regulates the size of their endosomes, the expression of the Draper engulfment receptor, and the clearance of neuronal debris in an axotomy model. We propose that APP proteins represent a novel family of neuroglial signaling factors required for adult brain homeostasis., The Amyloid Precursor Protein (APP) is strongly implicated in the etiology of Alzheimer’s disease, but what is its physiological function in the adult brain? This study in Drosophila shows that APP mediates interactions between neurons and glial cells to ensure healthy brain homeostasis.
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- 2020
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42. Generation of neuronal diversity from common progenitors via Notch signaling in the cerebellum
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Tingting Zhang, Tengyuan Liu, Natalia Mora, Justine Guegan, Mathilde Bertrand, Ximena Contreras, Andi H. Hansen, Carmen Streicher, Marica Anderle, Luca Tiberi, Simon Hippenmeyer, Bassem A. Hassan
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- 2020
- Full Text
- View/download PDF
43. A neuroscientific approach to increase gender equality
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Nicolas Renier, Violetta Zujovic, Cécile Delarasse, Bassem A. Hassan, Alexandra Durr, Nathalie George, Alexandra Auffret, Charlotte Rosso, Michel Thiebaut de Schotten, Magali Dumont, Eric Burguière, Emmanuelle Volle, Christiane Schreiweis, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Neurologie et thérapeutique expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Neurobiologie des processus adaptatifs (NPA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Cogimage, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Institut de la Vision, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Université de Bordeaux (UB), Sorbonne Université (SU), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physiologie de la Perception et de l'Action (LPPA), Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), GEORGE, Nathalie, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Social Psychology ,Cognitive Neuroscience ,Sexism ,MEDLINE ,[SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior ,Experimental and Cognitive Psychology ,Cognitive neuroscience ,050105 experimental psychology ,03 medical and health sciences ,Behavioral Neuroscience ,[SCCO]Cognitive science ,0302 clinical medicine ,5. Gender equality ,Humans ,0501 psychology and cognitive sciences ,10. No inequality ,ComputingMilieux_MISCELLANEOUS ,Gender equality ,Stereotyping ,Gender identity ,[SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior ,[SCCO.NEUR]Cognitive science/Neuroscience ,05 social sciences ,[SCCO.NEUR] Cognitive science/Neuroscience ,Academies and Institutes ,Gender Identity ,16. Peace & justice ,[SHS.GENRE] Humanities and Social Sciences/Gender studies ,3. Good health ,Leadership ,[SCCO.PSYC] Cognitive science/Psychology ,[SCCO.PSYC]Cognitive science/Psychology ,France ,Psychology ,[SHS.GENRE]Humanities and Social Sciences/Gender studies ,030217 neurology & neurosurgery ,Cognitive psychology - Abstract
International audience; To the Editor-Gender inequality is prevalent in many countries and cultures, and it persists despite our awareness of it and the policies some countries have put in place to combat it. France, for example, offers significant opportunities to enable women to handle both career and personal life: it provides a social healthcare system that was ranked No. 1 by the World Health Organization in 2000, a legal framework promoting gender equality 1 , and relatively accessible and affordable childcare and scholastic infrastructure. Herein lies the paradox: despite France having a strong reputation for providing a favourable social and professional context, French women still lag behind French men in their careers. One of the main reasons gender inequality persists despite this supportive infrastructure is the perpetuation of implicit biases and gender stereotypes. These shape the way we behave, our ability to recognize unequal treatment, the willingness of disadvantaged individuals to speak up, and even the research conducted in institutions that have been raising awareness of gender inequalities in science since 2001 2,3
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- 2019
44. Decision letter: Presynaptic developmental plasticity allows robust sparse wiring of the Drosophila mushroom body
- Author
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Bassem A. Hassan
- Subjects
biology ,Mushroom bodies ,Developmental plasticity ,Drosophila (subgenus) ,biology.organism_classification ,Neuroscience - Published
- 2019
45. Induction of granule and Purkinje cells from primary cultured mouse cerebellar progenitors
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Tengyuan Liu, Tingting Zhang, Bassem A. Hassan, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Gestionnaire, HAL Sorbonne Université 5
- Subjects
Calbindins ,Cerebellum ,Science (General) ,PAX6 Transcription Factor ,Cellular differentiation ,Cell Culture Techniques ,Mice, Transgenic ,Biology ,Time-Lapse Imaging ,Calbindin ,General Biochemistry, Genetics and Molecular Biology ,Q1-390 ,Purkinje Cells ,03 medical and health sciences ,0302 clinical medicine ,SOX2 ,Protocol ,medicine ,Animals ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Progenitor cell ,Cells, Cultured ,030304 developmental biology ,Progenitor ,Neurons ,Microscopy ,0303 health sciences ,General Immunology and Microbiology ,Stem Cells ,General Neuroscience ,Cell Differentiation ,Cell Biology ,Embryonic stem cell ,3. Good health ,Cell biology ,medicine.anatomical_structure ,nervous system ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Cell culture ,Stem cell ,030217 neurology & neurosurgery ,Neuroscience - Abstract
Summary The architecturally stereotypical structure of cerebellum is ideal for investigating the generation of neuronal diversity, but in vitro models for assessing early cerebellar progenitor differentiation were lacking. Here, we report a detailed protocol for long-term in vitro generation of Pax6+ granule cells and Calbindin+ Purkinje cells from common Sox2+ embryonic cerebellar progenitors. We describe the procedure for dissecting mouse cerebellar anlage, cell seeding, and tamoxifen-induced labeling of progenitor cells, followed by time-lapse video recording of clonal expansion and neuronal differentiation. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2021)., Graphical abstract, Highlights • Embryonic mouse cerebellar anlage isolation and primary cell culture • Induced differentiation of cerebellar progenitors into granule and Purkinje cells • Long-term time-lapse recording of clonal expansion and neuronal differentiation • Identification of granule neurons and Purkinje neurons in single progenitor clones, The architecturally stereotypical structure of cerebellum is ideal for investigating the generation of neuronal diversity, but in vitro models for assessing early cerebellar progenitor differentiation were lacking. Here, we report a detailed protocol for long-term in vitro generation of Pax6+ granule cells and Calbindin+ Purkinje cells from common Sox2+ embryonic cerebellar progenitors. We describe the procedure for dissecting mouse cerebellar anlage, cell seeding, and tamoxifen-induced labeling of progenitor cells, followed by time-lapse video recording of clonal expansion and neuronal differentiation.
- Published
- 2021
46. Single-cell resolution view of the transcriptional landscape of developingDrosophilaeye
- Author
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Natalia Danda, Sara Fonseca Topp, Agnes Wong-Chung, Radoslaw K. Ejsmont, Natalia Mora Garcia, Bassem A. Hassan, and Grace Houser
- Subjects
Retina ,medicine.anatomical_structure ,Gene expression ,Regulator ,medicine ,Computational biology ,Progenitor cell ,Biology ,Developmental biology ,Transcription factor ,Gene ,Recombineering - Abstract
Faithful and reliable quantification of gene expression at a single-cell level is an outstanding challenge in developmental biology. Most existing approaches face a trade-off between the signal to noise ratio, resolution, and sensitivity. Here, we present a novel approach for in situ quantification of gene expression in a developing tissue. Our pipeline combines computational prediction of transcription factor targets, gene tagging, fluorescent reporter imaging, state-of-the-art image analysis, and automated cell-type identification. By applying this approach to identify the sequence of quantitative changes in gene expression which govern the development of theDrosophilaneural retina, we demonstrate the feasibility of our method. We analyze the targets of Atonal (Ato), a transcription factor that controls the transition from eye disc progenitor cell to photoreceptor neurons. We utilized recombineering and genomic engineering to tag all predicted Ato targets with novel transcriptional reporters. These reporters enable following the expression of both regulator and regulated genes to accurately quantify their expression levels in individual cells. Our complete computational pipeline identifies nuclei in the eye discs and detects different states of cells as they progress through differentiation. Based on detailed gene expression analysis, our technique revealed genes likely to be direct Ato targets and provided insight into how gene expression changes drive the specification of photoreceptors.
- Published
- 2019
47. Decision letter: EphrinB2 regulates VEGFR2 during dendritogenesis and hippocampal circuitry development
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Bassem A. Hassan and Injune Kim
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biology ,VEGF receptors ,biology.protein ,Hippocampal formation ,Neuroscience - Published
- 2019
48. Decision letter: VEGF/VEGFR2 signaling regulates hippocampal axon branching during development
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Bassem A. Hassan and Injune Kim
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Axonal branching ,VEGF receptors ,biology.protein ,Biology ,Hippocampal formation ,Neuroscience - Published
- 2019
49. A neurodevelopmental origin of behavioral individuality
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Suchetana Bias Dutta, Bassem A. Hassan, Mathias F. Wernet, Liz Hellbruegge, Guangda Liu, Peter Robin Hiesinger, Andrew Straw, Lisa M. Fenk, Radoslaw K. Ejsmont, Maheva Andriatsilavo, and Gerit A. Linneweber
- Subjects
0303 health sciences ,education.field_of_study ,Developmental noise ,media_common.quotation_subject ,Population ,Asymmetry ,Object (philosophy) ,Nature versus nurture ,03 medical and health sciences ,Monocular deprivation ,0302 clinical medicine ,Variation (linguistics) ,Causal link ,Psychology ,education ,Neuroscience ,030217 neurology & neurosurgery ,030304 developmental biology ,media_common - Abstract
The genome versus experience, or “Nature versus Nurture”, debate has dominated our understanding of individual behavioral variation. A third factor, namely variation in complex behavior potentially due to non-heritable “developmental noise” in brain development, has been largely ignored. Using the Drosophila vinegar fly we demonstrate a causal link between variation in brain wiring due to developmental noise, and behavioral individuality. A population of visual system neurons called DCNs shows non-heritable, inter-individual variation in right/left wiring asymmetry, and control object orientation in freely walking flies. We show that DCN wiring asymmetry predicts an individual’s object responses: the greater the asymmetry, the better the individual orients. Silencing DCNs abolishes correlations between anatomy and behavior, while inducing visual asymmetry via monocular deprivation “rescues” object orientation in DCN-symmetric individuals.One Sentence SummaryNon-heritable individual variation in neural circuit development underlies individual variability in behavior.
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- 2019
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50. A neurodevelopmental origin of behavioral individuality in the
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Gerit Arne, Linneweber, Maheva, Andriatsilavo, Suchetana Bias, Dutta, Mercedes, Bengochea, Liz, Hellbruegge, Guangda, Liu, Radoslaw K, Ejsmont, Andrew D, Straw, Mathias, Wernet, Peter Robin, Hiesinger, and Bassem A, Hassan
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Drosophila melanogaster ,Neurogenesis ,Orientation ,Individuality ,Animals ,Brain ,Genetic Variation ,Visual Pathways ,Visual Fields - Abstract
The genome versus experience dichotomy has dominated understanding of behavioral individuality. By contrast, the role of nonheritable noise during brain development in behavioral variation is understudied. Using
- Published
- 2019
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