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6. Ecrg4 expression and its product augurin in the choroid plexus: Impact on fetal brain development, cerebrospinal fluid homeostasis and neuroprogenitor cell response to CNS injury

Author

Gonzalez, AM, Podvin, S, Lin, SY, Miller, MC, Botfield, H, Leadbeater, WE, Roberton, A, Dang, X, Knowling, SE, Cardenas-Galindo, E, Donahue, JE, Stopa, EG, Johanson, CE, Coimbra, R, Eliceiri, BP, and Baird, A

Abstract

Background: The content and composition of cerebrospinal fluid (CSF) is determined in large part by the choroid plexus (CP) and specifically, a specialized epithelial cell (CPe) layer that responds to, synthesizes, and transports peptide hormones into and out of CSF. Together with ventricular ependymal cells, these CPe relay homeostatic signals throughout the central nervous system (CNS) and regulate CSF hydrodynamics. One new candidate signal is augurin, a newly recognized 14 kDa protein that is encoded by esophageal cancer related gene-4 (Ecrg4), a putative tumor suppressor gene whose presence and function in normal tissues remains unexplored and enigmatic. The aim of this study was to explore whether Ecrg4 and its product augurin, can be implicated in CNS development and the response to CNS injury.Methods: Ecrg4 gene expression in CNS and peripheral tissues was studied by in situ hybridization and quantitative RT-PCR. Augurin, the protein encoded by Ecrg4, was detected by immunoblotting, immunohistochemistry and ELISA. The biological consequence of augurin over-expression was studied in a cortical stab model of rat CNS injury by intra-cerebro-ventricular injection of an adenovirus vector containing the Ecrg4 cDNA. The biological consequences of reduced augurin expression were evaluated by characterizing the CNS phenotype caused by Ecrg4 gene knockdown in developing zebrafish embryos.Results: Gene expression and immunohistochemical analyses revealed that, the CP is a major source of Ecrg4 in the CNS and that Ecrg4 mRNA is predominantly localized to choroid plexus epithelial (CPe), ventricular and central canal cells of the spinal cord. After a stab injury into the brain however, both augurin staining and Ecrg4 gene expression decreased precipitously. If the loss of augurin was circumvented by over-expressing Ecrg4 in vivo, BrdU incorporation by cells in the subependymal zone decreased. Inversely, gene knockdown of Ecrg4 in developing zebrafish embryos caused increased proliferation of GFAP-positive cells and induced a dose-dependent hydrocephalus-like phenotype that could be rescued by co-injection of antisense morpholinos with Ecrg4 mRNA.Conclusion: An unusually elevated expression of the Ecrg4 gene in the CP implies that its product, augurin, plays a role in CP-CSF-CNS function. The results are all consistent with a model whereby an injury-induced decrease in augurin dysinhibits target cells at the ependymal-subependymal interface. We speculate that the ability of CP and ependymal epithelium to alter the progenitor cell response to CNS injury may be mediated, in part by Ecrg4. If so, the canonic control of its promoter by DNA methylation may implicate epigenetic mechanisms in neuroprogenitor fate and function in the CNS. © 2011 Gonzalez et al; licensee BioMed Central Ltd.

Published
2011

14. Hydrodynamics, Fungal Physiology, and Morphology

Author

Serrano-Carreón, L., Galindo, E., Rocha-Valadéz, J. A., Holguín-Salas, A., Corkidi, G., Scheper, Thomas, Series editor, Belkin, Shimshon, Series editor, Doran, Pauline M., Series editor, Gu, Man Bock, Series editor, Hu, Wei-Shou, Series editor, Mattiasson, Bo, Series editor, Nielsen, Jens, Series editor, Seitz, Harald, Series editor, Stephanopoulos, Gregory N., Series editor, Ulber, Roland, Series editor, Zeng, An-Ping, Series editor, Zhong, Jian-Jiang, Series editor, Zhou, Weichang, Series editor, Krull, Rainer, editor, and Bley, Thomas, editor

Published
2015
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15. The translational genetics of ADHD and related phenotypes in model organisms.

Author

Cabana-Domínguez, J., Antón-Galindo, E., Fernàndez-Castillo, N., Singgih, E.L., O'Leary, A., Norton, W.H., Strekalova, T., Schenck, A., Reif, A., Lesch, K.P., Slattery, D., Cormand, B., Cabana-Domínguez, J., Antón-Galindo, E., Fernàndez-Castillo, N., Singgih, E.L., O'Leary, A., Norton, W.H., Strekalova, T., Schenck, A., Reif, A., Lesch, K.P., Slattery, D., and Cormand, B.

Abstract

01 januari 2023, Item does not contain fulltext, Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder resulting from the interaction between genetic and environmental risk factors. It is well known that ADHD co-occurs frequently with other psychiatric disorders due, in part, to shared genetics factors. Although many studies have contributed to delineate the genetic landscape of psychiatric disorders, their specific molecular underpinnings are still not fully understood. The use of animal models can help us to understand the role of specific genes and environmental stimuli-induced epigenetic modifications in the pathogenesis of ADHD and its comorbidities. The aim of this review is to provide an overview on the functional work performed in rodents, zebrafish and fruit fly and highlight the generated insights into the biology of ADHD, with a special focus on genetics and epigenetics. We also describe the behavioral tests that are available to study ADHD-relevant phenotypes and comorbid traits in these models. Furthermore, we have searched for new models to study ADHD and its comorbidities, which can be useful to test potential pharmacological treatments.

Published
2023

25. Metal Fused Filament Fabrication of AlSi10Mg Aluminum Alloy.

Author

Galindo, E., Maric, M., Postigo, A. Avalos, Walker, A., Conlon, M., Azari, K., and Brochu, M.

Subjects
FABRICATION (Manufacturing), ALUMINUM alloys, MICROSTRUCTURE, ELECTRIC conductivity, MECHANICAL behavior of materials
Abstract

Metal-fused filament fabrication (MF3), which is a variation of the conventional fused filament fabrication (FFF), has recently gained interest due to its distinctive process flexibility and rapid prototyping capability to produce metallic parts. With respect to the additive manufacturing (AM) of aluminum alloys, most efforts have been centered on laser powder bed fusion technologies, with limited activities focused on binder-based processes due to challenges in the sintering of aluminum powders. With respect to MF3, one challenge for fabricating metallic components is the appropriate selection of a binder mixture, enabling the extrusion of a filament with high metallic volume content. In this paper, a mixture of biodegradable aliphatic polyester thermoplastic is used as a binder phase to act as the carrier for AlSi10Mg alloy powders. [ABSTRACT FROM AUTHOR]

Published
2023
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26. Online Sauter Diameter Measurement of Air Bubbles and Oil Drops in Stirred Bioreactors by Using Hough Transform

Author

Vega-Alvarado, L., Cordova, M. S., Taboada, B., Galindo, E., Corkidi, G., Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Dough, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Campilho, Aurélio, editor, and Kamel, Mohamed, editor

Published
2004
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27. Electromagnetic Transition Strengths in 104CD and 101AG and Their Interpretation within the Interacting Boson (Fermion) Plus Broken Pair Model

Author

Jungclaus, A., Müller, G. A., Galindo, E., Yordanov, O., Hausmann, M., Kast, D., Lieb, K. P., Brant, S., Krstic, V., Vretenar, D., Algora, A., Brandolini, F., De Angelis, G., De Poli, M., Fahlander, C., Gadea, A., Martinez, T., Napoli, D. R., Dewald, A., Peusquens, R., Tiesler, H., Gorska, M., Grawe, H., Nazarewicz, Witold, editor, and Vretenar, Dario, editor

Published
2002
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36. Deficiency of the ywhaz gene, involved in neurodevelopmental disorders, alters brain activity and behaviour in zebrafish

Author

Antón-Galindo E, Dalla Vecchia E, Orlandi JG, Castro G, Gualda EJ, Young AMJ, Guasch-Piqueras M, Arenas C, Herrera-Úbeda C, Garcia-Fernàndez J, Aguado F, Loza-Alvarez P, Cormand B, Norton WHJ, and Fernandez N

Abstract

Genetic variants in YWHAZ contribute to psychiatric disorders such as autism spectrum disorder and schizophrenia, and have been related to an impaired neurodevelopment in humans and mice. Here, we have used zebrafish to investigate the mechanisms by which YWHAZ contributes to neurodevelopmental disorders. We observed that ywhaz expression was pan-neuronal during developmental stages and restricted to Purkinje cells in the adult cerebellum, cells that are described to be reduced in number and size in autistic patients. We then performed whole-brain imaging in wild-type and ywhaz CRISPR/Cas9 knockout (KO) larvae and found altered neuronal activity and connectivity in the hindbrain. Adult ywhaz KO fish display decreased levels of monoamines in the hindbrain and freeze when exposed to novel stimuli, a phenotype that can be reversed with drugs that target monoamine neurotransmission. These findings suggest an important role for ywhaz in establishing neuronal connectivity during development and modulating both neurotransmission and behaviour in adults.

Published
2022

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