218 results on '"Abigail S. Tucker"'
Search Results
2. Identification and characterisation of spontaneous mutations causing deafness from a targeted knockout programme
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Morag A. Lewis, Neil J. Ingham, Jing Chen, Selina Pearson, Francesca Di Domenico, Sohinder Rekhi, Rochelle Allen, Matthew Drake, Annelore Willaert, Victoria Rook, Johanna Pass, Thomas Keane, David J. Adams, Abigail S. Tucker, Jacqueline K. White, and Karen P. Steel
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Spontaneous mutations ,Large-scale mutagenesis programme ,Deafness ,Progressive hearing loss ,Non-segregating phenotypes ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background Mice carrying targeted mutations are important for investigating gene function and the role of genes in disease, but off-target mutagenic effects associated with the processes of generating targeted alleles, for instance using Crispr, and culturing embryonic stem cells, offer opportunities for spontaneous mutations to arise. Identifying spontaneous mutations relies on the detection of phenotypes segregating independently of targeted alleles, and having a broad estimate of the level of mutations generated by intensive breeding programmes is difficult given that many phenotypes are easy to miss if not specifically looked for. Here we present data from a large, targeted knockout programme in which mice were analysed through a phenotyping pipeline. Such spontaneous mutations segregating within mutant lines may confound phenotypic analyses, highlighting the importance of record-keeping and maintaining correct pedigrees. Results Twenty-five lines out of 1311 displayed different deafness phenotypes that did not segregate with the targeted allele. We observed a variety of phenotypes by Auditory Brainstem Response (ABR) and behavioural assessment and isolated eight lines showing early-onset severe progressive hearing loss, later-onset progressive hearing loss, low frequency hearing loss, or complete deafness, with vestibular dysfunction. The causative mutations identified include deletions, insertions, and point mutations, some of which involve new genes not previously associated with deafness while others are new alleles of genes known to underlie hearing loss. Two of the latter show a phenotype much reduced in severity compared to other mutant alleles of the same gene. We investigated the ES cells from which these lines were derived and determined that only one of the 8 mutations could have arisen in the ES cell, and in that case, only after targeting. Instead, most of the non-segregating mutations appear to have occurred during breeding of mutant mice. In one case, the mutation arose within the wildtype colony used for expanding mutant lines. Conclusions Our data show that spontaneous mutations with observable effects on phenotype are a common side effect of intensive breeding programmes, including those underlying targeted mutation programmes. Such spontaneous mutations segregating within mutant lines may confound phenotypic analyses, highlighting the importance of record-keeping and maintaining correct pedigrees.
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- 2022
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3. Eda controls the size of the enamel knot during incisor development
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Lucie Horakova, Linda Dalecka, Oldrich Zahradnicek, Katerina Lochovska, Herve Lesot, Renata Peterkova, Abigail S. Tucker, and Maria Hovorakova
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tabby mouse ,mouse incisor ,shh expression ,rudiment ,tooth development ,Physiology ,QP1-981 - Abstract
Ectodysplasin (Eda) plays important roles in both shaping the developing tooth and establishing the number of teeth within the tooth row. Sonic hedgehog (Shh) has been shown to act downstream of Eda and is involved in the initiation of tooth development. Eda−/− mice possess hypoplastic and hypomineralized incisors and show changes in tooth number in the molar region. In the present study we used 3D reconstruction combined with expression analysis, cell lineage tracing experiments, and western blot analysis in order to investigate the formation of the incisor germs in Eda−/− mice. We show that a lack of functional Eda protein during early stages of incisor tooth germ development had minimal impact on development of the early expression of Shh in the incisor, a region proposed to mark formation of a rudimental incisor placode and act as an initiating signalling centre. In contrast, deficiency of Eda protein had a later impact on expression of Shh in the primary enamel knot of the functional tooth. Eda−/− mice had a smaller region where Shh was expressed, and a reduced contribution from Shh descendant cells. The reduction in the enamel knot led to the formation of an abnormal enamel organ creating a hypoplastic functional incisor. Eda therefore appears to influence the spatial formation of the successional signalling centres during odontogenesis.
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- 2023
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4. The interconnected relationships between middle ear bulla size, cavitation defects, and chronic otitis media revealed in a syndromic mouse model
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Juan M. Fons, Natalie J. Milmoe, Michael R. G. Dack, Leena Joshi, Hannah Thompson, and Abigail S. Tucker
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ear development ,congenital birth defect ,branchio-oto-renal syndrome ,cavitation ,basal cell hyperplasia ,Genetics ,QH426-470 - Abstract
High incidence of chronic otitis media is associated with human craniofacial syndromes, suggesting that defects in the formation of the middle ear and associated structures can have a knock-on effect on the susceptibility to middle ear inflammation. Patients with branchio-oto-renal (BOR) syndrome have several defects in the ear leading to both sensorineural and conductive hearing loss, including otitis media. 40% of BOR syndrome cases are due to Eya1 haploinsufficiency, with mouse models affecting Eya1, mimicking many of the defects found in patients. Here, we characterize the onset, consequences, and underlying causes of chronic otitis media in Eya1 heterozygous mice. Cavitation defects were evident in these mice from postnatal day (P)11 onwards, with mesenchyme around the promontory and attic regions of the middle ear space. This mesenchyme was still prominent in adult Eya1 heterozygous mice, while the wild-type littermates had fully aerated ears from P14 onwards. MicroCT analysis highlighted a significantly smaller bulla, confirming the link between bulla size defects and the ability of the mesenchyme to retract successfully. Otitis media was observed from P14, often presenting unilaterally, resulting in hyperplasia of the middle ear mucosa, expansion of secretory cells, defects in the motile cilia, and changes in basal epithelial cell markers. A high incidence of otitis media was identified in older mice but only associated with ears with retained mesenchyme. To understand the impact of the environment, the mouse line was rederived onto a super-clean environment. Cavitation defects were still evident at early stages, but these generally resolved over time, and importantly, no signs of otitis media were observed at 6 weeks. In conclusion, we show that a small bulla size is closely linked to defects in cavitation and the presence of retained mesenchyme. A delay in retraction of the mesenchyme predates the onset of otitis media, making the ears susceptible to its development. Early exposure to OM appears to exacerbate the cavitation defect, with mesenchyme evident in the middle ear throughout the animal’s life. This highlights that permanent damage to the middle ear can arise as a consequence of the early onset of OM.
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- 2022
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5. Endothelial cells during craniofacial development: Populating and patterning the head
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Hiba Asrar and Abigail S. Tucker
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angiogenesis ,vasculogenesis ,cell signalling ,vascular biology ,tooth ,gland ,Biotechnology ,TP248.13-248.65 - Abstract
Major organs and tissues require close association with the vasculature during development and for later function. Blood vessels are essential for efficient gas exchange and for providing metabolic sustenance to individual cells, with endothelial cells forming the basic unit of this complex vascular framework. Recent research has revealed novel roles for endothelial cells in mediating tissue morphogenesis and differentiation during development, providing an instructive role to shape the tissues as they form. This highlights the importance of providing a vasculature when constructing tissues and organs for tissue engineering. Studies in various organ systems have identified important signalling pathways crucial for regulating the cross talk between endothelial cells and their environment. This review will focus on the origin and migration of craniofacial endothelial cells and how these cells influence the development of craniofacial tissues. For this we will look at research on the interaction with the cranial neural crest, and individual organs such as the salivary glands, teeth, and jaw. Additionally, we will investigate the methods used to understand and manipulate endothelial networks during the development of craniofacial tissues, highlighting recent advances in this area.
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- 2022
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6. Genetic Variants in Protein Tyrosine Phosphatase Non-Receptor Type 23 Are Responsible for Mesiodens Formation
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Ploy Adisornkanj, Rajit Chanprasit, Steven Eliason, Juan M. Fons, Worrachet Intachai, Sissades Tongsima, Bjorn Olsen, Stefan T. Arold, Chumpol Ngamphiw, Brad A. Amendt, Abigail S. Tucker, and Piranit Kantaputra
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extra tooth ,PTPN23 ,mesiodentes ,mutation ,phosphatase ,protein expression ,Biology (General) ,QH301-705.5 - Abstract
A mesiodens is a supernumerary tooth located in the midline of the premaxilla. To investigate the genetic cause of mesiodens, clinical and radiographic examination were performed on 23 family members of a two-generation Hmong family. Whole exome sequencing (WES) or Sanger sequencing were performed in 22 family members and two unrelated Thai patients with mesiodens. WES in the Hmong family revealed a missense mutation (c.1807G>A;p.Glu603Lys) in PTPN23 in seven affected members and six unaffected members. The mode of inheritance was autosomal dominance with incomplete penetrance (53.84%). Two additional mutations in PTPN23, c.2248C>G;p.Pro750Ala and c.3298C>T;p.Arg1100Cys were identified in two unrelated patients with mesiodens. PTPN23 is a regulator of endosomal trafficking functioning to move activated membrane receptors, such as EGFR, from the endosomal sorting complex towards the ESCRT-III complex for multivesicular body biogenesis, lysosomal degradation, and subsequent downregulation of receptor signaling. Immunohistochemical study and RNAscope on developing mouse embryos showed broad expression of PTPN23 in oral tissues, while immunofluorescence showed that EGFR was specifically concentrated in the midline epithelium. Importantly, PTPN23 mutant protein was shown to have reduced phosphatase activity. In conclusion, mesiodens were associated with genetic variants in PTPN23, suggesting that mesiodens may form due to defects in endosomal trafficking, leading to disrupted midline signaling.
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- 2023
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7. Inhibition of Aurora Kinase B activity disrupts development and differentiation of salivary glands
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Abeer K. Shaalan, Tathyane H. N. Teshima, Abigail S. Tucker, and Gordon B. Proctor
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Cytology ,QH573-671 - Abstract
Abstract Little is known about the key molecules that regulate cell division during organogenesis. Here we determine the role of the cell cycle promoter aurora kinase B (AURKB) during development, using embryonic salivary glands (E-SGs) as a model. AURKB is a serine/threonine kinase that regulates key events in mitosis, which makes it an attractive target for tailored anticancer therapy. Many reports have elaborated on the role of AURKB in neoplasia and cancer; however, no previous study has shown its role during organ development. Our previous experiments have highlighted the essential requirement for AURKB during adult exocrine regeneration. To investigate if AURKB is similarly required for progression during embryonic development, we pharmacologically inhibited AURKB in developing submandibular glands (SMGs) at embryonic day (E)13.5 and E16.5, using the highly potent and selective drug Barasertib. Inhibition of AURKB interfered with the expansion of the embryonic buds. Interestingly, this effect on SMG development was also seen when the mature explants (E16.5) were incubated for 24 h with another cell cycle inhibitor Aphidicolin. Barasertib prompted apoptosis, DNA damage and senescence, the markers of which (cleaved caspase 3, γH2AX, SA-βgal and p21, respectively), were predominantly seen in the developing buds. In addition to a reduction in cell cycling and proliferation of the epithelial cells in response to AURKB inhibition, Barasertib treatment led to an excessive generation of reactive oxygen species (ROS) that resulted in downregulation of the acinar differentiation marker Mist1. Importantly, inhibition of ROS was able to rescue this loss of identity, with Mist1 expression maintained despite loss of AURKB. Together, these data identify AURKB as a key molecule in supporting embryonic development and differentiation, while inhibiting senescence-inducing signals during organogenesis.
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- 2021
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8. The Intertwined Evolution and Development of Sutures and Cranial Morphology
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Heather E. White, Anjali Goswami, and Abigail S. Tucker
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suture ,morphology ,development ,craniofacial ,evolution ,mammal ,Biology (General) ,QH301-705.5 - Abstract
Phenotypic variation across mammals is extensive and reflects their ecological diversification into a remarkable range of habitats on every continent and in every ocean. The skull performs many functions to enable each species to thrive within its unique ecological niche, from prey acquisition, feeding, sensory capture (supporting vision and hearing) to brain protection. Diversity of skull function is reflected by its complex and highly variable morphology. Cranial morphology can be quantified using geometric morphometric techniques to offer invaluable insights into evolutionary patterns, ecomorphology, development, taxonomy, and phylogenetics. Therefore, the skull is one of the best suited skeletal elements for developmental and evolutionary analyses. In contrast, less attention is dedicated to the fibrous sutural joints separating the cranial bones. Throughout postnatal craniofacial development, sutures function as sites of bone growth, accommodating expansion of a growing brain. As growth frontiers, cranial sutures are actively responsible for the size and shape of the cranial bones, with overall skull shape being altered by changes to both the level and time period of activity of a given cranial suture. In keeping with this, pathological premature closure of sutures postnatally causes profound misshaping of the skull (craniosynostosis). Beyond this crucial role, sutures also function postnatally to provide locomotive shock absorption, allow joint mobility during feeding, and, in later postnatal stages, suture fusion acts to protect the developed brain. All these sutural functions have a clear impact on overall cranial function, development and morphology, and highlight the importance that patterns of suture development have in shaping the diversity of cranial morphology across taxa. Here we focus on the mammalian cranial system and review the intrinsic relationship between suture development and morphology and cranial shape from an evolutionary developmental biology perspective, with a view to understanding the influence of sutures on evolutionary diversity. Future work integrating suture development into a comparative evolutionary framework will be instrumental to understanding how developmental mechanisms shaping sutures ultimately influence evolutionary diversity.
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- 2021
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9. Anatomy and Development of the Mammalian External Auditory Canal: Implications for Understanding Canal Disease and Deformity
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Mona Mozaffari, Robert Nash, and Abigail S. Tucker
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hearing ,deafness ,external ear ,ear canal ,ear deformities ,congenital ,Biology (General) ,QH301-705.5 - Abstract
The mammalian ear is made up of three parts (the outer, middle, and inner ear), which work together to transmit sound waves into neuronal signals perceived by our auditory cortex as sound. This review focuses on the often-neglected outer ear, specifically the external auditory meatus (EAM), or ear canal. Within our complex hearing pathway, the ear canal is responsible for funneling sound waves toward the tympanic membrane (ear drum) and into the middle ear, and as such is a physical link between the tympanic membrane and the outside world. Unique anatomical adaptations, such as its migrating epithelium and cerumen glands, equip the ear canal for its function as both a conduit and a cul-de-sac. Defects in development, or later blockages in the canal, lead to congenital or acquired conductive hearing loss. Recent studies have built on decades-old knowledge of ear canal development and suggest a novel multi-stage, complex and integrated system of development, helping to explain the mechanisms underlying congenital canal atresia and stenosis. Here we review our current understanding of ear canal development; how this biological lumen is made; what determines its location; and how its structure is maintained throughout life. Together this knowledge allows clinical questions to be approached from a developmental biology perspective.
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- 2021
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10. An Essential Requirement for Fgf10 in Pinna Extension Sheds Light on Auricle Defects in LADD Syndrome
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Yang Zhang, Juan M. Fons, Mohammad K. Hajihosseini, Tianyu Zhang, and Abigail S. Tucker
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ear development ,auricle ,congenital birth defect ,muscle ,fibroblast growth factor ,microtia ,Biology (General) ,QH301-705.5 - Abstract
The pinna (or auricle) is part of the external ear, acting to capture and funnel sound toward the middle ear. The pinna is defective in a number of craniofacial syndromes, including Lacrimo-auriculo-dento-digital (LADD) syndrome, which is caused by mutations in FGF10 or its receptor FGFR2b. Here we study pinna defects in the Fgf10 knockout mouse. We show that Fgf10 is expressed in both the muscles and forming cartilage of the developing external ear, with loss of signaling leading to a failure in the normal extension of the pinna over the ear canal. Conditional knockout of Fgf10 in the neural crest fails to recapitulate this phenotype, suggesting that the defect is due to loss of Fgf10 from the muscles, or that this source of Fgf10 can compensate for loss in the forming cartilage. The defect in the Fgf10 null mouse is driven by a reduction in proliferation, rather than an increase in cell death, which can be partially phenocopied by inhibiting cell proliferation in explant culture. Overall, we highlight the mechanisms that could lead to the phenotype observed in LADD syndrome patients and potentially explain the formation of similar low-set and cup shaped ears observed in other syndromes.
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- 2020
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11. Diverse Fate of an Enigmatic Structure: 200 Years of Meckel’s Cartilage
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Eva Svandova, Neal Anthwal, Abigail S. Tucker, and Eva Matalova
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jaw development ,craniofacial ,mammal evolution ,congenital birth defects ,chondrogenesis ,Biology (General) ,QH301-705.5 - Abstract
Meckel’s cartilage was first described by the German anatomist Johann Friedrich Meckel the Younger in 1820 from his analysis of human embryos. Two hundred years after its discovery this paper follows the development and largely transient nature of the mammalian Meckel’s cartilage, and its role in jaw development. Meckel’s cartilage acts as a jaw support during early development, and a template for the later forming jaw bones. In mammals, its anterior domain links the two arms of the dentary together at the symphysis while the posterior domain ossifies to form two of the three ear ossicles of the middle ear. In between, Meckel’s cartilage transforms to a ligament or disappears, subsumed by the growing dentary bone. Several human syndromes have been linked, directly or indirectly, to abnormal Meckel’s cartilage formation. Herein, the evolution, development and fate of the cartilage and its impact on jaw development is mapped. The review focuses on developmental and cellular processes that shed light on the mechanisms behind the different fates of this cartilage, examining the control of Meckel’s cartilage patterning, initiation and maturation. Importantly, human disorders and mouse models with disrupted Meckel’s cartilage development are highlighted, in order to understand how changes in this cartilage impact on later development of the dentary and the craniofacial complex as a whole. Finally, the relative roles of tissue interactions, apoptosis, autophagy, macrophages and clast cells in the removal process are discussed. Meckel’s cartilage is a unique and enigmatic structure, the development and function of which is starting to be understood but many interesting questions still remain.
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- 2020
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12. Balance Between Tooth Size and Tooth Number Is Controlled by Hyaluronan
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Natalia Sánchez, María Constanza González-Ramírez, Esteban G. Contreras, Angélica Ubilla, Jingjing Li, Anyeli Valencia, Andrés Wilson, Jeremy B. A. Green, Abigail S. Tucker, and Marcia Gaete
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successional tooth development ,cell orientation ,organogenesis ,activator-inhibitor ,molar development ,Physiology ,QP1-981 - Abstract
While the function of proteins and genes has been widely studied during vertebrate development, relatively little work has addressed the role of carbohydrates. Hyaluronan (HA), also known as hyaluronic acid, is an abundant carbohydrate in embryonic tissues and is the main structural component of the extracellular matrix of epithelial and mesenchymal cells. HA is able to absorb large quantities of water and can signal by binding to cell-surface receptors. During organ development and regeneration, HA has been shown to regulate cell proliferation, cell shape, and migration. Here, we have investigated the function of HA during molar tooth development in mice, in which, similar to humans, new molars sequentially bud off from a pre-existing molar. Using an ex vivo approach, we found that inhibiting HA synthesis in culture leads to a significant increase in proliferation and subsequent size of the developing molar, while the formation of sequential molars was inhibited. By cell shape analysis, we observed that inhibition of HA synthesis caused an elongation and reorientation of the major cell axes, indicating that disruption to cellular orientation and shape may underlie the observed phenotype. Lineage tracing demonstrated the retention of cells in the developing first molar (M1) at the expense of the generation of a second molar (M2). Our results highlight a novel role for HA in controlling proliferation, cell orientation, and migration in the developing tooth, impacting cellular decisions regarding tooth size and number.
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- 2020
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13. Development of the Vestibular Lamina in Human Embryos: Morphogenesis and Vestibule Formation
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Tengyang Qiu, Tathyane H. N. Teshima, Maria Hovorakova, and Abigail S. Tucker
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dental pathologies ,keratin ,epithelial differentiation ,apoptosis ,oral mucosa ,human development ,Physiology ,QP1-981 - Abstract
The vestibular lamina (VL) is a transient developmental structure that forms the lip furrow, creating a gap between the lips/cheeks and teeth (oral vestibule). Surprisingly, little is known about the development of the VL and its relationship to the adjacent dental lamina (DL), which forms the teeth. In some congenital disorders, such as Ellis-van Creveld (EVC) syndrome, development of the VL is disrupted and multiple supernumerary frenula form, physically linking the lips and teeth. Here, we assess the normal development of the VL in human embryos from 6.5 (CS19) to 13 weeks of development, showing the close relationship between the VL and DL, from initiation to differentiation. In the anterior lower region, the two structures arise from the same epithelial thickening. The VL then undergoes complex morphogenetic changes during development, forming a branched structure that separates to create the vestibule. Changing expression of keratins highlight the differentiation patterns in the VL, with fissure formation linked to the onset of filaggrin. Apoptosis is involved in removal of the central portion of the VL to create a broad furrow between the future cheek and gum. This research forms an essential base to further explore developmental defects in this part of the oral cavity.
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- 2020
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14. The TMJ Disc Is a Common Ancestral Feature in All Mammals, as Evidenced by the Presence of a Rudimentary Disc During Monotreme Development
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Neal Anthwal and Abigail S. Tucker
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TMJ disc ,monotreme ,mammalian evolution ,jaw joint ,evo devo ,muscle ,Biology (General) ,QH301-705.5 - Abstract
The novel mammalian jaw joint, known in humans as the temporomandibular joint or TMJ, is cushioned by a fibrocartilage disc. This disc is secondarily absent in therian mammals that have lost their dentition, such as giant anteaters and some baleen whales. The disc is also absent in all monotremes. However, it is not known if the absence in monotremes is secondary to the loss of dentition, or if it is an ancestral absence. We use museum held platypus and echidna histological sections to demonstrate that the developing monotreme jaw joint forms a disc primordium that fails to mature and become separated from the mandibular condyle. We then show that monotreme developmental anatomy is similar to that observed in transgenic mouse mutants with reduced cranial musculature. We therefore suggest that the absence of the disc on monotremes is a consequence of the changes in jaw musculature associated with the loss of adult teeth. Taken together, these data indicate that the ancestors of extant monotremes likely had a jaw joint disc, and that the disc evolved in the last common ancestor of all mammals.
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- 2020
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15. Q&A: Morphological insights into evolution
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Neal Anthwal and Abigail S. Tucker
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Biology (General) ,QH301-705.5 - Abstract
Abstract In this question and answer article we discuss how evolution shapes morphology (the shape and pattern of our bodies) but also how learning about morphology, and specifically how that morphology arises during development, can shed light on mechanisms that might allow change during evolution. For this we concentrate on recent findings from our lab on how the middle ear has formed in mammals.
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- 2017
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16. Epithelial topography for repetitive tooth formation
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Marcia Gaete, Juan Manuel Fons, Elena Mădălina Popa, Lemonia Chatzeli, and Abigail S. Tucker
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Successional tooth development ,Sox2 ,Sox9 ,Odontogenesis ,Organogenesis ,Science ,Biology (General) ,QH301-705.5 - Abstract
During the formation of repetitive ectodermally derived organs such as mammary glands, lateral line and teeth, the tissue primordium iteratively initiates new structures. In the case of successional molar development, new teeth appear sequentially in the posterior region of the jaw from Sox2+ cells in association with the posterior aspect of a pre-existing tooth. The sequence of molar development is well known, however, the epithelial topography involved in the formation of a new tooth is unclear. Here, we have examined the morphology of the molar dental epithelium and its development at different stages in the mouse in vivo and in molar explants. Using regional lineage tracing we show that within the posterior tail of the first molar the primordium for the second and third molar are organized in a row, with the tail remaining in connection with the surface, where a furrow is observed. The morphology and Sox2 expression of the tail retains characteristics reminiscent of the earlier stages of tooth development, such that position along the A-P axes of the tail correlates with different temporal stages. Sox9, a stem/progenitor cell marker in other organs, is expressed mainly in the suprabasal epithelium complementary with Sox2 expression. This Sox2 and Sox9 expressing molar tail contains actively proliferating cells with mitosis following an apico-basal direction. Snail2, a transcription factor implicated in cell migration, is expressed at high levels in the tip of the molar tail while E-cadherin and laminin are decreased. In conclusion, our studies propose a model in which the epithelium of the molar tail can grow by posterior movement of epithelial cells followed by infolding and stratification involving a population of Sox2+/Sox9+ cells.
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- 2015
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17. Activation of Pro-apoptotic Caspases in Non-apoptotic Cells During Odontogenesis and Related Osteogenesis
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Eva Svandova, Barbora Vesela, Abigail S. Tucker, and Eva Matalova
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caspase ,differentiation ,apoptosis ,tooth ,intramembranous ,bone ,Physiology ,QP1-981 - Abstract
Caspases are well known proteases in the context of inflammation and apoptosis. Recently, novel roles of pro-apoptotic caspases have been reported, including findings related to the development of hard tissues. To further investigate these emerging functions of pro-apoptotic caspases, the in vivo localisation of key pro-apoptotic caspases (-3,-6,-7,-8, and -9) was assessed, concentrating on the development of two neighbouring hard tissues, cells participating in odontogenesis (represented by the first mouse molar) and intramembranous osteogenesis (mandibular/alveolar bone). The expression of the different caspases within the developing tissues was correlated with the apoptotic status of the cells, to produce a picture of whether different caspases have potentially distinct, or overlapping non-apoptotic functions. The in vivo investigation was additionally supported by examination of caspases in an osteoblast-like cell line in vitro. Caspases-3,-7, and -9 were activated in apoptotic cells of the primary enamel knot of the first molar; however, caspase-7 and -8 activation was also associated with the non-apoptotic enamel epithelium at the same stage and later with differentiating/differentiated odontoblasts and ameloblasts. In the adjacent bone, active caspases-7 and -8 were present abundantly in the prenatal period, while the appearance of caspases-3,-6, and -9 was marginal. Perinatally, caspases-3 and -7 were evident in some osteoclasts and osteoblastic cells, and caspase-8 was abundant mostly in osteoclasts. In addition, postnatal activation of caspases-7 and -8 was retained in osteocytes. The results provide a comprehensive temporo-spatial pattern of pro-apoptotic caspase activation, and demonstrate both unique and overlapping activation in non-apoptotic cells during development of the molar tooth and mandibular/alveolar bone. The importance of caspases in osteogenic pathways is highlighted by caspase inhibition in osteoblast-like cells, which led to a significant decrease in osteocalcin expression, supporting a role in hard tissue cell differentiation.
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- 2018
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18. Dynamic relationship of the epithelium and mesenchyme during salivary gland initiation: the role of Fgf10
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Kirsty L. Wells, Marcia Gaete, Eva Matalova, Danny Deutsch, David Rice, and Abigail S. Tucker
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Salivary gland ,Fgf10 ,Epithelial–mesenchymal interactions ,Recombination ,GFP ,Science ,Biology (General) ,QH301-705.5 - Abstract
Summary Salivary glands provide an excellent model for the study of epithelial–mesenchymal interactions. We have looked at the interactions involved in the early initiation and development of murine salivary glands using classic recombination experiments and knockout mice. We show that salivary gland epithelium, at thickening and initial bud stages, is able to direct salivary gland development in non-gland pharyngeal arch mesenchyme at early stages. The early salivary gland epithelium is therefore able to induce gland development in non-gland tissue. This ability later shifts to the mesenchyme, with non-gland epithelium, such as from the limb bud, able to form a branching gland when combined with pseudoglandular stage gland mesenchyme. This shift appears to involve Fgf signalling, with signals from the epithelium inducing Fgf10 in the mesenchyme. Fgf10 then signals back to the epithelium to direct gland down-growth and bud development. These experiments highlight the importance of epithelial–mesenchymal signalling in gland initiation, controlling where, when and how many salivary glands form.
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- 2013
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19. Correction: Hearing Loss in a Mouse Model of 22q11.2 Deletion Syndrome.
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Jennifer C. Fuchs, Fhatarah A. Zinnamon, Ruth R. Taylor, Sarah Ivins, Peter J. Scambler, Andrew Forge, Abigail S. Tucker, and Jennifer F. Linden
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Medicine ,Science - Published
- 2014
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20. Dynamic relationship of the epithelium and mesenchyme during salivary gland initiation: the role of Fgf10
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Kirsty L. Wells, Marcia Gaete, Eva Matalova, Danny Deutsch, David Rice, and Abigail S. Tucker
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Science ,Biology (General) ,QH301-705.5 - Published
- 2014
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21. Wnt signaling from Gli1-expressing apical stem/progenitor cells is essential for the coordination of tooth root development
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Rupali Lav, Jan Krivanek, Neal Anthwal, and Abigail S. Tucker
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Genetics ,Cell Biology ,Biochemistry ,Developmental Biology - Published
- 2023
22. Getting out of a mammalian egg: the egg tooth and caruncle of the echidna
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Jane C Fenelon, Alistair R. Evans, Michael Pyne, Stephen D. Johnston, Neal Anthwal, Abigail S. Tucker, Abbie Bennetts, and Marilyn B. Renfree
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Premaxilla ,biology ,Egg tooth ,Histology ,Anatomy ,Cell Biology ,biology.organism_classification ,Monotreme ,stomatognathic diseases ,medicine.anatomical_structure ,stomatognathic system ,Evagination ,embryonic structures ,Echidna ,medicine ,Pouch ,Nasal capsule ,Molecular Biology ,Developmental Biology - Abstract
In the short-beaked echidna, Tachyglossus aculeatus, after an initial period of in utero development, the egg is laid in the pouch and incubated for 10 days. During this time, the fetuses develop an egg tooth and caruncle to help them hatch. However, there are only a few historical references that describe the development of the monotreme egg tooth. Using unprecedented access to echidna pre- and post-hatching tissues, the egg tooth and caruncle were assessed by micro-CT, histology and immunofluorescence, to map the changes at the morphological and molecular level. Unlike mammalian tooth germs that develop by invagination of a placode, the echidna egg tooth developed by evagination, similar to that of the first teeth in some reptiles. The egg tooth ankylosed to the premaxilla, rather than forming a mammalian thecodont attachment, with loss of the egg tooth post-hatching associated with high levels of odontoclasts, and apoptosis. The caruncle formed as a separate mineralisation from the adjacent nasal capsule, and as observed in birds and turtles, the nasal region epithelium expressed markers of cornification. Together, this highlights that the monotreme egg tooth shares many similarities with reptilian teeth, suggesting that this tooth is conserved from a common ancestor of mammals and reptiles.
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- 2023
23. Mechanisms driving vestibular lamina formation and opening in the mouse
- Author
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Tengyang Qiu and Abigail S. Tucker
- Subjects
Histology ,Cell Biology ,Anatomy ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Developmental Biology - Abstract
The vestibular lamina (VL) forms as an epithelial outgrowth parallel to the dental lamina (DL) in the oral cavity. During late development, it opens to create a furrow that divides the dental tissue from the cheeks and lips and is known as the vestibule. Defects in this process lead to failure in the separation of the teeth from the lips and cheeks, including the presence of multiple frenula. In this paper, the development of the VL is followed in the mouse, from epithelial placode in the embryo to postnatal opening and vestibule formation. During early outgrowth, differential proliferation controls the curvature of the VL as it extends under the forming incisors. Apoptosis plays a role in thinning the deepest part of the lamina, while terminal differentiation of the epithelium, highlighted by the expression of loricrin and flattening of the nuclei, predates the division of the VL into two to create the vestibule. Development in the mouse is compared to the human VL, with respect to the relationship of the VL to the DL, VL morphology and mechanisms of opening. Overall, this paper provides insight into an understudied part of the oral anatomy, shedding light on how defects could form in this region.
- Published
- 2022
24. Pedomorphosis in the ancestry of marsupial mammals
- Author
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Heather E. White, Abigail S. Tucker, Vincent Fernandez, Roberto Portela Miguez, Lionel Hautier, Anthony Herrel, Daniel J. Urban, Karen E. Sears, and Anjali Goswami
- Subjects
General Agricultural and Biological Sciences ,General Biochemistry, Genetics and Molecular Biology - Published
- 2023
25. Molecular profiling of the vestibular lamina highlights a key role for Hedgehog signalling
- Author
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Tengyang Qiu, Barbora Hutečková, Maisa Seppala, Martyn T. Cobourne, Zhi Chen, Mária Hovořáková, Marcela Buchtová, and Abigail S. Tucker
- Subjects
Molecular Biology ,Developmental Biology - Abstract
The vestibular lamina (VL) forms the oral vestibule, creating a gap between the teeth, lips and cheeks. In a number of ciliopathies, formation of the vestibule is defective, leading to the creation of multiple frenula. In contrast to the neighbouring dental lamina, which forms the teeth, little is known about the genes that pattern the VL. Here, we establish a molecular signature for the usually non-odontogenic VL in mice and highlight several genes and signalling pathways that may play a role in its development. For one of these, the Sonic hedgehog (Shh) pathway, we show that co-receptors Gas1, Cdon and Boc are highly expressed in the VL and act to enhance the Shh signal from the forming incisor region. In Gas1 mutant mice, expression of Gli1 was disrupted and the VL epithelium failed to extend due to a loss of proliferation. This defect was exacerbated in Boc/Gas1 double mutants and could be phenocopied using cyclopamine in culture. Signals from the forming teeth, therefore, control development of the VL, coordinating the development of the dentition and the oral cavity.
- Published
- 2023
26. Evolution and development of the mammalian jaw joint: Making a novel structure
- Author
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Neal Anthwal and Abigail S. Tucker
- Subjects
Ecology, Evolution, Behavior and Systematics ,Developmental Biology - Abstract
A jaw joint between the squamosal and dentary is a defining feature of mammals and is referred to as the temporomandibular joint (TMJ) in humans. Driven by changes in dentition and jaw musculature, this new joint evolved early in the mammalian ancestral lineage and permitted the transference of the ancestral jaw joint into the middle ear. The fossil record demonstrates the steps in the cynodont lineage that led to the acquisition of the TMJ, including the expansion of the dentary bone, formation of the coronoid process, and initial contact between the dentary and squamosal. From a developmental perspective, the components of the TMJ form through tissue interactions of muscle and skeletal elements, as well as through interaction between the jaw and the cranial base, with the signals involved in these interactions being both biomechanical and biochemical. In this review, we discuss the development of the TMJ in an evolutionary context. We describe the evolution of the TMJ in the fossil record and the development of the TMJ in embryonic development. We address the formation of key elements of the TMJ and how knowledge from developmental biology can inform our understanding of TMJ evolution.
- Published
- 2022
27. Cryptophthalmos, dental anomalies, oral vestibule defect, and a novel FREM2 mutation
- Author
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Worrachet Intachai, Abigail S. Tucker, Sissades Tongsima, Chumpol Ngamphiw, Nutsuchar Wangtiraumnuay, Piranit Nik Kantaputra, and Bjorn R. Olsen
- Subjects
Adult ,Cryptophthalmos ,Vestibular lamina ,Compound heterozygosity ,medicine.disease_cause ,Frameshift mutation ,Mutant protein ,Exome Sequencing ,Genetics ,medicine ,Humans ,Eye Abnormalities ,Gene ,Genetics (clinical) ,Basement membrane ,Extracellular Matrix Proteins ,Eyelashes ,Mutation ,Tooth Abnormalities ,Chemistry ,Eyelids ,medicine.disease ,Molecular biology ,medicine.anatomical_structure ,Female ,Mouth Abnormalities - Abstract
FREM2 is a member of the FREM2–FRAS1–FREM1 protein complex which contributes to epithelial–mesenchymal coupling. We report a Thai woman with cryptophthalmos, dental anomalies, and oral vestibule defect. A compound heterozygous mutation (c.6499C>T; p.Arg2167Trp and c.641_642del; p.Glu214GlyfsTer135) in the FREM2 gene was identified. The frameshift variant p.Glu214GlyfsTer135 is de novo and novel. It is predicted to result in the loss of most of the functional domains. The p.Arg2167Trp mutation was predicted to disrupt both Ca2+ binding and conformational change. The Arg2167Trp mutant protein has been shown to cause partial loss of function, decrease its interaction with FREM1 and result in impaired function of the FRAS1–FREM2–FREM1 complex. Frem2 was shown to be expressed in the developing tooth and vestibular lamina. It is hypothesized that these mutations resulted in aberration of the FRAS1–FREM2–FREM1 protein complex, resulting in loss of nephronectin, basement membrane disruption, and abnormal epithelial–mesenchymal interactions leading to dental and oral vestibule malformations.
- Published
- 2021
28. Mutations in LRP6 highlight the role of WNT signaling in oral exostoses and dental anomalies
- Author
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Piranit Kantaputra, Peeranat Jatooratthawichot, Kanoknart Chintakanon, Worrachet Intachai, Prapat Pradermdutsadeeporn, Ploy Adisornkanj, Sissades Tongsima, Chumpol Ngamphiw, Bjorn Olsen, Abigail S. Tucker, and James R. Ketudat Cairns
- Subjects
Otorhinolaryngology ,Tooth, Supernumerary ,Tooth Abnormalities ,Low Density Lipoprotein Receptor-Related Protein-6 ,Mutation ,Odontoma ,Humans ,Cell Biology ,General Medicine ,Exostoses ,General Dentistry ,Wnt Signaling Pathway - Abstract
The objective of this study was to investigate molecular etiologies of oral exostoses and dental anomalies in 14 patients from eight families.Oral and radiographic examinations were performed on every patient. Whole exome and Sanger sequencing were performed on DNA of the patients, the unaffected parents and unaffected siblings. LRP6 mutant proteins were modeled and analyzed.Five mutations in LRP6, including four missense (p.Glu72Lys, p.Lys82Asn, Tyr418His, and p.Ile773Val) and one nonsense mutation (p.Arg32Ter), were identified. These mutations have not been reported to be associated with dental anomalies or oral exostoses. Oral features included a variety of oral exostoses (7 of the 14 patients), root defects (6 of the 14 patients), and tooth agenesis (5 of the 14 patients). Less common dental anomalies included microdontia, tooth fusion, odontomas, and mesiodens. Analysis of the protein models of the five LRP6 mutations shed light on their likely impact on LRP6 protein structure and function.Fourteen patients with five LRP6 mutations, including two recurrent mutations and three novel ones, are reported. Our study shows for the first time that mutations in LRP6 are associated with mesiodens, fusion of teeth, odontomas, microdontia, long roots, molars with unseparated roots, and taurodontism.
- Published
- 2022
29. Nuclear receptor Nr5a2 promotes diverse connective tissue fates in the jaw
- Author
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Hung-Jhen Chen, Lindsey Barske, Jared C. Talbot, Olivia M. Dinwoodie, Ryan R. Roberts, D’Juan T. Farmer, Christian Jimenez, Amy E. Merrill, Abigail S. Tucker, and J. Gage Crump
- Subjects
Cell Biology ,Molecular Biology ,General Biochemistry, Genetics and Molecular Biology ,Developmental Biology - Published
- 2023
30. Comparing development and regeneration in the submandibular gland highlights distinct mechanisms
- Author
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Tathyane Harumi Nakajima Teshima, Marcia Gaete, Mohammad K. Hajihosseini, Gordon Proctor, Abigail S. Tucker, and Lemonia Chatzeli
- Subjects
Male ,0301 basic medicine ,Histology ,Organogenesis ,Mesenchyme ,Submandibular Gland ,duct ,Biology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,stomatognathic system ,medicine ,Animals ,Regeneration ,remodelling ,ligation ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Original Paper ,FGF10 ,Fgf10 ,Salivary gland ,adult ,Regeneration (biology) ,Gene Expression Regulation, Developmental ,SOX9 Transcription Factor ,Cell Biology ,Original Papers ,Submandibular gland ,Epithelium ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,repair ,Female ,Anatomy ,Fibroblast Growth Factor 10 ,030217 neurology & neurosurgery ,Homeostasis ,Sox9 ,Developmental Biology - Abstract
A common question in organ regeneration is the extent to which regeneration recapitulates embryonic development. To investigate this concept, we compared the expression of two highly interlinked and essential genes for salivary gland development, Sox9 and Fgf10, during submandibular gland development, homeostasis and regeneration. Salivary gland duct ligation/deligation model was used as a regenerative model. Fgf10 and Sox9 expression changed during regeneration compared to homeostasis, suggesting that these key developmental genes play important roles during regeneration, however, significantly both displayed different patterns of expression in the regenerating gland compared to the developing gland. Regenerating glands, which during homeostasis had very few weakly expressing Sox9‐positive cells in the striated/granular ducts, displayed elevated expression of Sox9 within these ducts. This pattern is in contrast to embryonic development, where Sox9 expression was absent in the proximally developing ducts. However, similar to the elevated expression at the distal tip of the epithelium in developing salivary glands, regenerating glands displayed elevated expression in a subpopulation of acinar cells, which during homeostasis expressed Sox9 at lower levels. A shift in expression of Fgf10 was observed from a widespread mesenchymal pattern during organogenesis to a more limited and predominantly epithelial pattern during homeostasis in the adult. This restricted expression in epithelial cells was maintained during regeneration, with no clear upregulation in the surrounding mesenchyme, as might be expected if regeneration recapitulated development. As both Fgf10 and Sox9 were upregulated in proximal ducts during regeneration, this suggests that the positive regulation of Sox9 by Fgf10, essential during development, is partially reawakened during regeneration using this model. Together these data suggest that developmentally important genes play a key role in salivary gland regeneration but do not precisely mimic the roles observed during development., A common question in organ regeneration is the extent to which regeneration recapitulates embryonic development. To investigate this concept, we compared the expression of two highly interlinked and essential genes for salivary gland development, Sox9 and Fgf10, during submandibular gland development, homeostasis and regeneration. Our data suggest that developmentally important genes play a key role in salivary gland regeneration but do not precisely mimic the roles observed during development.
- Published
- 2021
31. A mesenchymal to epithelial switch in Fgf10 expression specifies an evolutionary-conserved population of ionocytes in salivary glands
- Author
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Olivier Mauduit, Marit H. Aure, Vanessa Delcroix, Liana Basova, Amrita Srivastava, Takeshi Umazume, Jacqueline W. Mays, Saverio Bellusci, Abigail S. Tucker, Mohammad K. Hajihosseini, Matthew P. Hoffman, and Helen P. Makarenkova
- Subjects
salivary gland ,Epithelial Cells ,Forkhead Transcription Factors ,duct cells ,Developmental biology [CP] ,General Biochemistry, Genetics and Molecular Biology ,single-cell RNA sequencing ,Salivary Glands ,stomatognathic diseases ,Mice ,FGF10 ,Foxi1 ,niche cells ,submandibular gland ,ionocytes ,FGFR2b signaling ,Animals ,CFTR ,Receptor, Fibroblast Growth Factor, Type 2 ,Fibroblast Growth Factor 10 ,Signal Transduction - Abstract
Fibroblast growth factor 10 (FGF10) is well established as a mesenchyme-derived growth factor and a critical regulator of fetal organ development in mice and humans. Using a single-cell RNA sequencing (RNA-seq) atlas of salivary gland (SG) and a tamoxifen inducible Fgf10CreERT2:R26-tdTomato mouse, we show that FGF10pos cells are exclusively mesenchymal until postnatal day 5 (P5) but, after P7, there is a switch in expression and only epithelial FGF10pos cells are observed after P15. Further RNA-seq analysis of sorted mesenchymal and epithelial FGF10pos cells shows that the epithelial FGF10pos population express the hallmarks of ancient ionocyte signature Forkhead box i1 and 2 (Foxi1, Foxi2), Achaete-scute homolog 3 (Ascl3), and the cystic fibrosis transmembrane conductance regulator (Cftr). We propose that epithelial FGF10pos cells are specialized SG ionocytes located in ducts and important for the ionic modification of saliva. In addition, they maintain FGF10-dependent gland homeostasis via communication with FGFR2bpos ductal and myoepithelial cells.
- Published
- 2022
32. Expanding genotypic and phenotypic spectrums of LTBP3 variants in dental anomalies and short stature syndrome
- Author
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Piranit Kantaputra, Yeliz Guven, Tugba Kalayci, Pelin Karaca Özer, Wannakamon Panyarak, Worrachet Intachai, Bjorn Olsen, Bruce M. Carlson, Oranud Praditsap, Sissades Tongsima, Chumpol Ngamphiw, Peeranat Jatooratthawichot, Abigail S. Tucker, and James R. Ketudat Cairns
- Subjects
Male ,Phenotype ,Latent TGF-beta Binding Proteins ,Amelogenesis Imperfecta ,Tooth Abnormalities ,Transforming Growth Factor beta ,Genetics ,Humans ,Dwarfism ,Osteochondrodysplasias ,Genetics (clinical) - Abstract
Mutations in LTBP3 are associated with Dental Anomalies and Short Stature syndrome (DASS; MIM 601216), which is characterized by hypoplastic type amelogenesis imperfecta, hypodontia, underdeveloped maxilla, short stature, brachyolmia, aneurysm and dissection of the thoracic aorta. Here we report a novel (p.Arg545ProfsTer22) and a recurrent (c.3107-2A G) LTBP3 variants, in a Turkish family affected with DASS. The proband, who carried compound heterozygous variant c.3107-2A G, p.Arg545ProfsTer22, was most severely affected with DASS. The proband's father, who carried the heterozygous variant c.3107-2A G had short stature and prognathic mandible. The mother and brother of the proband carried the heterozygous variant p.Arg545ProfsTer22, but only the mother showed any DASS characteristics. The c.3107-2A G and the p.Arg545ProfsTer22 variants are expected to result in abnormal LTPB3 protein, failure of TGFβ-LAP-LTBP3 complex formation, and subsequent disruption of TGFβ secretion and activation. This is the first report of heterozygous carriers of LTBP3 variants showing phenotypes. The new findings of DASS found in this family include taurodontism, single-rooted molars, abnormal dentin, calcified dental pulp blood vessels, prognathic mandible, failure of mandibular tooth eruption, interatrial septal aneurysm, secundum atrial septal defect, tricuspid valve prolapse, and a recurrent glenohumeral joint dislocation.
- Published
- 2022
33. Caspase Inhibition Affects the Expression of Autophagy-Related Molecules in Chondrocytes
- Author
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Eva Matalová, Alice Ramesova, Abigail S. Tucker, Eva Švandová, Adela Kratochvilova, and Barbora Veselá
- Subjects
0301 basic medicine ,Proteases ,Biomedical Engineering ,Physical Therapy, Sports Therapy and Rehabilitation ,Chondrocyte ,Mice ,03 medical and health sciences ,Chondrocytes ,0302 clinical medicine ,Gene expression ,Autophagy ,medicine ,Animals ,Immunology and Allergy ,Clinical Research papers ,Caspase ,PIK3CG ,biology ,Chemistry ,Chondrogenesis ,Caspase Inhibitors ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Apoptosis ,Caspases ,030220 oncology & carcinogenesis ,biology.protein - Abstract
Objective. Caspases, cysteine proteases traditionally associated with apoptosis and inflammation, have recently been identified as important regulators of autophagy and reported within the growth plate, a cartilaginous part of the developing bone. The aim of this research was to identify novel autophagy-related molecules affected by inhibition of pro-apoptotic caspases in chondrocytes. Design. Chondrocyte micromasses derived from mouse limb buds were treated with pharmacological inhibitors of caspases. Autophagy-related gene expression was examined and possible novel molecules were confirmed by real-time polymerase chain reaction and immunocytofluorescence. Individual caspases inhibitors were used to identify the effect of specific caspases. Results. Chondrogenesis accompanied by caspase activation and autophagy progression was confirmed in micromass cultures. Expression of several autophagy-associated genes was significantly altered in the caspases inhibitors treated groups with the most prominent decrease for Pik3cg and increase of Tnfsf10. The results showed the specific pro-apoptotic caspases that play a role in these effects. Importantly, use of caspase inhibitors mimicked changes triggered by an autophagy stimulator, rapamycin, linking loss of caspase activity to an increase in autophagy. Conclusion. Caspase inhibition significantly affects regulation of autophagy-related genes in chondrocytes cultures. Detected markers are of importance in diagnostics and thus the data presented here open new perspectives in the field of cartilage development and degradation.
- Published
- 2020
34. Developmental mechanisms driving complex tooth shape in reptiles
- Author
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Hana Dosedelova, Tomáš Zikmund, Jana Dumková, Jozef Kaiser, Marcela Buchtová, Marek Hampl, Martina Gregorovicova, Jan Krivanek, Oldrich Zahradnicek, David Sedmera, Abigail S. Tucker, Marie Šulcová, and Michaela Kavkova
- Subjects
0301 basic medicine ,Cell ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Microscopy, Electron, Transmission ,stomatognathic system ,FGF4 ,medicine ,Animals ,Dental Enamel ,Cytoskeleton ,Enamel paint ,Inner enamel epithelium ,Gene Expression Regulation, Developmental ,Reptiles ,Lipid Droplets ,Actins ,Epithelium ,Cell biology ,stomatognathic diseases ,030104 developmental biology ,medicine.anatomical_structure ,visual_art ,visual_art.visual_art_medium ,Ultrastructure ,Odontogenesis ,Tooth ,Nucleus ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Background In mammals, odontogenesis is regulated by transient signaling centers known as enamel knots (EKs), which drive the dental epithelium shaping. However, the developmental mechanisms contributing to formation of complex tooth shape in reptiles are not fully understood. Here, we aim to elucidate whether signaling organizers similar to EKs appear during reptilian odontogenesis and how enamel ridges are formed. Results Morphological structures resembling the mammalian EK were found during reptile odontogenesis. Similar to mammalian primary EKs, they exhibit the presence of apoptotic cells and no proliferating cells. Moreover, expression of mammalian EK-specific molecules (SHH, FGF4, and ST14) and GLI2-negative cells were found in reptilian EK-like areas. 3D analysis of the nucleus shape revealed distinct rearrangement of the cells associated with enamel groove formation. This process was associated with ultrastructural changes and lipid droplet accumulation in the cells directly above the forming ridge, accompanied by alteration of membranous molecule expression (Na/K-ATPase) and cytoskeletal rearrangement (F-actin). Conclusions The final complex shape of reptilian teeth is orchestrated by a combination of changes in cell signaling, cell shape, and cell rearrangement. All these factors contribute to asymmetry in the inner enamel epithelium development, enamel deposition, ultimately leading to the formation of characteristic enamel ridges.
- Published
- 2020
35. Paedomorphosis at the Origin of Marsupial Mammals
- Author
-
Heather E. White, Abigail S. Tucker, Vincent Fernandez, Roberto Portela Miguez, Lionel Hautier, Anthony Herrel, Daniel J. Urban, Karen E. Sears, and Anjali Goswami
- Subjects
History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2022
36. Salivary Gland Development in Culture
- Author
-
Marcia Gaete, Tathyane H. N. Teshima, Lemonia Chatzeli, and Abigail S. Tucker
- Published
- 2021
37. Salivary Gland Development in Culture
- Author
-
Marcia, Gaete, Tathyane H N, Teshima, Lemonia, Chatzeli, and Abigail S, Tucker
- Subjects
Mesoderm ,Mice ,Organ Culture Techniques ,Submandibular Gland ,Morphogenesis ,Animals ,Epithelial Cells ,Epithelium ,Salivary Glands - Abstract
Salivary glands are branching organs which develop by bud and cleft formation to create an organ with a large surface area. The epithelium and mesenchyme signal back and forth to control this branching process, with additional cues provided by the parasympathetic nerves and blood vessels that surround the developing branches. This branching morphogenesis can be recapitulated successfully in organ culture , allowing access to the tissue to follow development and manipulate the tissue interactions, and signals. To culture glands, the filter-grid method has been widely used, allowing the development of salivary glands cultured as a whole organ, or the gland epithelium in isolation, or with the surrounding craniofacial tissue in a cranial slice. Here, we describe the methods for each approach and show the applicability of culturing glands from a wide variety of species: mouse , snake, and human. The resulting samples and data from these cultures can be employed for morphological and molecular analysis, with some examples described in this chapter, bringing valuable knowledge to our understanding of branching morphogenesis.
- Published
- 2021
38. Editorial: Contemporary Models in Ectodermal Organ Development, Maintenance and Regeneration
- Author
-
Maisa Seppala and Abigail S. Tucker
- Subjects
Physiology ,business.industry ,gland ,Regeneration (biology) ,Organ development ,tongue ,Physiology (medical) ,ectodermal organ ,QP1-981 ,Medicine ,tooth ,business ,development ,Neuroscience ,palate - Published
- 2021
39. Collateral damage: Identification and characterisation of spontaneous mutations causing deafness from a targeted knockout programme
- Author
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David J. Adams, Johanna C. Pass, J. Chen, A. Willaert, S. Rekhi, Abigail S. Tucker, M. Drake, Karen P. Steel, Selina Pearson, R. Allen, N. A. Ingham, V. Rook, M. A. Lewis, Jacqui White, F. Di Domenico, and Thomas M. Keane
- Subjects
Genetics ,Targeted Mutation ,Identification (biology) ,Disease ,Allele ,Biology ,Gene ,Embryonic stem cell ,Phenotype ,Function (biology) - Abstract
Mice carrying targeted mutations are important for investigating gene function and the role of genes in disease, but the process of culturing embryonic stem cells during the making of a targeted allele offers opportunities for spontaneous mutations to arise. Identifying spontaneous mutations relies on the detection of phenotypes segregating independently of targeted alleles, and many phenotypes are easy to miss if not specifically looked for. Here we present data from a large, targeted knockout programme in which mice were analysed through a phenotyping pipeline. Twenty-five lines out of 1311 displayed different deafness phenotypes that did not segregate with the targeted allele. We have identified 8 different mutations causing deafness in 16 of these 25 lines and characterised the resulting phenotypes. Our data show that spontaneous mutations with observable effects on phenotype are a common side effect of intensive breeding programmes, including those underlying targeted mutation programmes.
- Published
- 2021
40. Getting out of an egg: Merging of tooth germs to create an egg tooth in the snake
- Author
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Oldrich Zahradnicek, Eraqi R. Khannoon, Marcia Gaete, Abigail S. Tucker, Marcela Buchtová, Hussein Bandali, Juan Manuel Fons, Marie Landová, and Joy M. Richman
- Subjects
0301 basic medicine ,Orthodontics ,Large tooth ,Dentition ,Egg tooth ,Tooth Germ ,Snakes ,Single tooth ,Biology ,Oral cavity ,stomatognathic diseases ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,stomatognathic system ,embryonic structures ,Animals ,Tooth ,Potential mechanism ,030217 neurology & neurosurgery ,Tooth Germs ,Developmental Biology - Abstract
Background The egg tooth is a vital structure allowing hatchlings to escape from the egg. In squamates (snakes and lizards), the egg tooth is a real tooth that develops within the oral cavity at the top of the upper jaw. Most squamates have a single large midline egg tooth at hatching, but a few families, such as Gekkonidae, have two egg teeth. In snakes the egg tooth is significantly larger than the rest of the dentition and is one of the first teeth to develop. Results We follow the development of the egg tooth in four snake species and show that the single egg tooth is formed by two tooth germs. These two tooth germs are united at the midline and grow together to produce a single tooth. In culture, this merging can be perturbed to give rise to separate smaller teeth, confirming the potential of the developing egg tooth to form two teeth. Conclusions Our data agrees with previous hypotheses that during evolution one potential mechanism to generate a large tooth is through congrescence of multiple tooth germs and suggests that the ancestors of snakes could have had two egg teeth.
- Published
- 2019
41. Molar Bud-to-Cap Transition Is Proliferation Independent
- Author
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Rupali Lav, Shuntaro Yamada, Abigail S. Tucker, Jingjing Li, and Jeremy B. Green
- Subjects
0301 basic medicine ,Molar ,Pediatric Research Initiative ,1.1 Normal biological development and functioning ,Mesenchyme ,morphogenesis ,Odontogenic Epithelium ,Mesoderm ,developmental biology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Underpinning research ,Pregnancy ,cell biology ,medicine ,Animals ,Developmental ,General Dentistry ,Tooth Germs ,Cell Proliferation ,Pediatric ,morphometrics ,Transition (genetics) ,Chemistry ,tooth development ,Gene Expression Regulation, Developmental ,Tooth Germ ,Research Reports ,Biological ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Dentistry ,Congenital Structural Anomalies ,Odontogenesis ,Female ,basal constriction ,030217 neurology & neurosurgery - Abstract
Tooth germs undergo a series of dynamic morphologic changes through bud, cap, and bell stages, in which odontogenic epithelium continuously extends into the underlying mesenchyme. During the transition from the bud stage to the cap stage, the base of the bud flattens and then bends into a cap shape whose edges are referred to as “cervical loops.” Although genetic mechanisms for cap formation have been well described, little is understood about the morphogenetic mechanisms. Computer modeling and cell trajectory tracking have suggested that the epithelial bending is driven purely by differential cell proliferation and adhesion in different parts of the tooth germ. Here, we show that, unexpectedly, inhibition of cell proliferation did not prevent bud-to-cap morphogenesis. We quantified cell shapes and actin and myosin distributions in different parts of the tooth epithelium at the critical stages and found that these are consistent with basal relaxation in the forming cervical loops and basal constriction around enamel knot at the center of the cap. Inhibition of focal adhesion kinase, which is required for basal constriction in other systems, arrested the molar explant morphogenesis at the bud stage. Together, these results show that the bud-to-cap transition is largely proliferation independent, and we propose that it is driven by classic actomyosin-driven cell shape–dependent mechanisms. We discuss how these results can be reconciled with the previous models and data.
- Published
- 2019
42. Dual Sympathetic Input into Developing Salivary Glands
- Author
-
Tathyane Harumi Nakajima Teshima, Abigail S. Tucker, and Silvia Vanessa Lourenço
- Subjects
0301 basic medicine ,Sympathetic Nervous System ,Tyrosine 3-Monooxygenase ,Submandibular Gland ,Biology ,Neuronal signaling ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Branching morphogenesis ,Basic Helix-Loop-Helix Transcription Factors ,medicine ,Animals ,Humans ,Progenitor cell ,General Dentistry ,Neurons ,Catecholaminergic ,Hydroxydopamine ,Tyrosine hydroxylase ,Salivary gland ,030206 dentistry ,Submandibular ganglion ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure - Abstract
Neuronal signaling is known to be required for salivary gland development, with parasympathetic nerves interacting with the surrounding tissues from early stages to maintain a progenitor cell population and control morphogenesis. In contrast, postganglionic sympathetic nerves arrive late in salivary gland development to perform a secretory function; however, no previous report has shown their role during development. Here, we show that a subset of neuronal cells within the parasympathetic submandibular ganglion (PSG) express the catecholaminergic marker tyrosine hydroxylase (TH) in developing murine and human submandibular glands. This sympathetic phenotype coincided with the expression of transcription factor Hand2 within the PSG from the bud stage (E12.5) of mouse embryonic salivary gland development. Hand2 was previously associated with the decision of neural crest cells to become sympathetic in other systems, suggesting a role in controlling neuronal fate in the salivary gland. The PSG therefore provides a population of TH-expressing neurons prior to the arrival of the postganglionic sympathetic axons from the superior cervical ganglion at E15.5. In culture, in the absence of nerves from the superior cervical ganglion, these PSG-derived TH neurons were clearly evident forming a network around the gland. Chemical ablation of dopamine receptors in explant culture with the neurotoxin 6-hydroxydopamine at early stages of gland development resulted in specific loss of the TH-positive neurons from the PSG, and subsequent branching was inhibited. Taken altogether, these results highlight for the first time the detailed developmental time course of TH-expressing neurons during murine salivary gland development and suggest a role for these neurons in branching morphogenesis.
- Published
- 2019
43. Craniofacial transitions: the role of EMT and MET during head development
- Author
-
Natalie J. Milmoe and Abigail S. Tucker
- Subjects
Epithelial-Mesenchymal Transition ,Head (linguistics) ,Mesenchyme ,Population ,Cell fate determination ,Biology ,Epithelium ,Skeletal tissue ,Mesoderm ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,medicine ,Animals ,Humans ,Craniofacial ,education ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,Neural crest ,Cell Differentiation ,medicine.anatomical_structure ,Neural Crest ,Organ Specificity ,Vertebrates ,Head ,Neuroscience ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Within the developing head, tissues undergo cell-fate transitions to shape the forming structures. This starts with the neural crest, which undergoes epithelial-to-mesenchymal transition (EMT) to form, amongst other tissues, many of the skeletal tissues of the head. In the eye and ear, these neural crest cells then transform back into an epithelium, via mesenchymal-to-epithelial transition (MET), highlighting the flexibility of this population. Elsewhere in the head, the epithelium loses its integrity and transforms into mesenchyme. Here, we review these craniofacial transitions, looking at why they happen, the factors that trigger them, and the cell and molecular changes they involve. We also discuss the consequences of aberrant EMT and MET in the head.
- Published
- 2021
44. Anatomy and Development of the Mammalian External Auditory Canal: Implications for Understanding Canal Disease and Deformity
- Author
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Robert Nash, Mona Mozaffari, and Abigail S. Tucker
- Subjects
0301 basic medicine ,Meatus ,Review ,Auditory cortex ,ear canal ,03 medical and health sciences ,Cell and Developmental Biology ,0302 clinical medicine ,deafness ,external ear ,medicine ,Outer ear ,otorhinolaryngologic diseases ,Inner ear ,Ear canal ,030223 otorhinolaryngology ,lcsh:QH301-705.5 ,Sound (medical instrument) ,business.industry ,ear deformities ,congenital ,Cell Biology ,Anatomy ,medicine.disease ,Conductive hearing loss ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,hearing ,Middle ear ,sense organs ,business ,Developmental Biology - Abstract
The mammalian ear is made up of three parts (the outer, middle, and inner ear), which work together to transmit sound waves into neuronal signals perceived by our auditory cortex as sound. This review focuses on the often-neglected outer ear, specifically the external auditory meatus (EAM), or ear canal. Within our complex hearing pathway, the ear canal is responsible for funneling sound waves toward the tympanic membrane (ear drum) and into the middle ear, and as such is a physical link between the tympanic membrane and the outside world. Unique anatomical adaptations, such as its migrating epithelium and cerumen glands, equip the ear canal for its function as both a conduit and a cul-de-sac. Defects in development, or later blockages in the canal, lead to congenital or acquired conductive hearing loss. Recent studies have built on decades-old knowledge of ear canal development and suggest a novel multi-stage, complex and integrated system of development, helping to explain the mechanisms underlying congenital canal atresia and stenosis. Here we review our current understanding of ear canal development; how this biological lumen is made; what determines its location; and how its structure is maintained throughout life. Together this knowledge allows clinical questions to be approached from a developmental biology perspective.
- Published
- 2021
45. Coordinated labio-lingual asymmetries in dental and bone development create a symmetrical acrodont dentition
- Author
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Oldrich Zahradnicek, Abigail S. Tucker, Michaela Kavkova, Marie Šulcová, Tomáš Zikmund, Jana Dumková, Marcela Buchtová, and Jozef Kaiser
- Subjects
Science ,Cervical loop ,Biology ,Article ,stomatognathic system ,Dentin ,medicine ,Animals ,Body patterning ,Bone Development ,Multidisciplinary ,Enamel paint ,Dentition ,Enamel organ ,Lizards ,Pleurodont ,Anatomy ,Acrodont ,stomatognathic diseases ,Odontoblast ,medicine.anatomical_structure ,Jaw ,visual_art ,visual_art.visual_art_medium ,Odontogenesis ,Medicine ,Tooth - Abstract
Organs throughout the body develop both asymmetrically and symmetrically. Here, we assess how symmetrical teeth in reptiles can be created from asymmetrical tooth germs. Teeth of lepidosaurian reptiles are mostly anchored to the jaw bones by pleurodont ankylosis, where the tooth is held in place on the labial side only. Pleurodont teeth are characterized by significantly asymmetrical development of the labial and lingual sides of the cervical loop, which later leads to uneven deposition of hard tissue. On the other hand, acrodont teeth found in lizards of the Acrodonta clade (i.e. agamas, chameleons) are symmetrically ankylosed to the jaw bone. Here, we have focused on the formation of the symmetrical acrodont dentition of the veiled chameleon (Chamaeleo calyptratus). Intriguingly, our results revealed distinct asymmetries in morphology of the labial and lingual sides of the cervical loop during early developmental stages, both at the gross and ultrastructural level, with specific patterns of cell proliferation and stem cell marker expression. Asymmetrical expression of ST14 was also observed, with a positive domain on the lingual side of the cervical loop overlapping with the SOX2 domain. In contrast, micro-CT analysis of hard tissues revealed that deposition of dentin and enamel was largely symmetrical at the mineralization stage, highlighting the difference between cervical loop morphology during early development and differentiation of odontoblasts throughout later odontogenesis. In conclusion, the early asymmetrical development of the enamel organ seems to be a plesiomorphic character for all squamate reptiles, while symmetrical and precisely orchestrated deposition of hard tissue during tooth formation in acrodont dentitions probably represents a novelty in the Acrodonta clade.
- Published
- 2020
46. Epithelial dynamics shed light on the mechanisms underlying ear canal defects
- Author
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Steve Connor, Abigail S. Tucker, Juan Manuel Fons, Dean Malik, Abigail R. Marshall, Nicholas D. E. Greene, and Mona Mozaffari
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External ear ,Human Development ,Biology ,Epithelium ,03 medical and health sciences ,Mice ,0302 clinical medicine ,medicine ,otorhinolaryngologic diseases ,Animals ,Humans ,Ear canal ,Molecular Biology ,Sound wave ,030304 developmental biology ,0303 health sciences ,Premature Closure ,Cell Differentiation ,Epithelial Cells ,Aplasia ,Anatomy ,Severe hearing loss ,Hearing loss ,medicine.disease ,Canal atresia ,Meatal plate ,DNA-Binding Proteins ,Disease Models, Animal ,medicine.anatomical_structure ,Periderm ,Middle ear ,Encephalitis ,Mutant Proteins ,sense organs ,030217 neurology & neurosurgery ,Ear Canal ,Developmental Biology ,Transcription Factors - Abstract
Defects in ear canal development can cause severe hearing loss as sound waves fail to reach the middle ear. Here, we reveal new mechanisms that control human canal development and highlight for the first time the complex system of canal closure and reopening. These processes can be perturbed in mutant mice and in explant culture, mimicking the defects associated with canal atresia. The more superficial part of the canal forms from an open primary canal that closes and then reopens. In contrast, the deeper part of the canal forms from an extending solid meatal plate that opens later. Closure and fusion of the primary canal was linked to loss of periderm, with failure in periderm formation in Grhl3 mutant mice associated with premature closure of the canal. Conversely, inhibition of cell death in the periderm resulted in an arrest of closure. Once closed, re-opening of the canal occurred in a wave, triggered by terminal differentiation of the epithelium. Understanding these complex processes involved in canal development sheds light on the underlying causes of canal atresia., Highlighted Article: We reveal new mechanisms that control development of the ear canal and highlight for the first time the complex system of canal closure and reopening.
- Published
- 2020
47. A comparison of metrics for quantifying cranial suture complexity
- Author
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Anjali Goswami, Julien Clavel, Heather E White, Abigail S. Tucker, Department of Life Sciences, The Natural History Museum [London] (NHM), Centre for Craniofacial and Regenerative Biology [London, UK], King's College London Guy's Hospital [UK], Division of Biosciences, University College of London [London] (UCL), Équipe 6 - Paléontologie, Paléoécologie, Paléobiogéographie, Évolution (P3E), Laboratoire d'Ecologie des Hydrosystèmes Naturels et Anthropisés (LEHNA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0106 biological sciences ,skull ,Future studies ,Computer science ,Biomedical Engineering ,Biophysics ,mammal ,Bioengineering ,010603 evolutionary biology ,01 natural sciences ,Biochemistry ,Fractal dimension ,Biomaterials ,Complexity index ,03 medical and health sciences ,symbols.namesake ,Box counting ,Extant taxon ,Suture (anatomy) ,morphology ,Animals ,030304 developmental biology ,0303 health sciences ,Sutures ,morphometrics ,suture ,business.industry ,Spectral density ,Pattern recognition ,Cranial Sutures ,Benchmarking ,Fractals ,Fourier transform ,symbols ,Artificial intelligence ,Life Sciences–Mathematics interface ,[SDE.BE]Environmental Sciences/Biodiversity and Ecology ,complexity ,business ,Research Article ,Biotechnology - Abstract
Cranial sutures play critical roles in facilitating postnatal skull development and function. The diversity of function is reflected in the highly variable suture morphology and complexity. Suture complexity has seldom been studied, resulting in little consensus on the most appropriate approach for comparative, quantitative analyses. Here, we provide the first comprehensive comparison of current approaches for quantifying suture morphology, using a wide range of two-dimensional suture outlines across extinct and extant mammals (n= 79). Five complexity metrics (sinuosity index (SI), suture complexity index (SCI), fractal dimension (FD) box counting, FD madogram and a windowed short-time Fourier transform with power spectrum density (PSD) calculation) were compared with each other and with the shape variation in the dataset. Analyses of suture shape demonstrate that the primary axis of variation captured attributes other than complexity, supporting the use of a complexity metric over raw shape data for sutural complexity analyses. Each approach captured different aspects of complexity. PSD successfully discriminates different sutural features, such as looping patterns and interdigitation amplitude and number, while SCI best-captured variation in interdigitation number alone. Therefore, future studies should consider the relevant attributes for their question when selecting a metric for comparative analysis of suture variation, function and evolution.
- Published
- 2020
48. Characteristics of aquaporin 1, 3, and 5 expression during early murine salivary gland development
- Author
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Milena Monteiro de Souza, Tathyane Harumi Nakajima Teshima, Silvia Vanessa Lourenço, Fernanda de Paula, Marcello Menta Simonsen Nico, Abigail S. Tucker, and Cláudia Malheiros Coutinho-Camillo
- Subjects
0301 basic medicine ,Saliva ,Histology ,Morphogenesis ,Aquaporin ,Biology ,Aquaporins ,Salivary Glands ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Organ Culture Techniques ,stomatognathic system ,medicine ,Animals ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Original Paper ,Salivary gland ,Embryogenesis ,Myoepithelial cell ,Cell Biology ,Embryo, Mammalian ,Epithelium ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Aquaporin 1 ,Anatomy ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Aquaporins (AQPs) are essential to coordinate the transit of water and ions through the cell membrane. In salivary glands (SGs), AQPs have been associated with saliva formation, facilitating water absorption through the epithelium during the formation of hypotonic saliva, which is then secreted into the oral cavity. Different members of the AQP family have been suggested to play distinct roles during embryonic development, highlighted by their specific expression patterns. Here, we have investigated the expression patterns of AQP-1, AQP-3 and AQP-5 by immunofluorescence at key stages of salivary gland development, utilising cultured mouse embryonic submandibular (SMG) and sublingual (SLG) glands. The expression of AQPs was compared to a mitotic marker, phospho-histone 3 (PH3), a myoepithelial marker, smooth muscle actin (SMA), and a vascular marker, CD31. Qualitative analysis revealed that AQP-1 and AQP-3 were primarily expressed during the earlier phases of SG morphogenesis and were associated with cells undergoing mitotic processes (PH3-positive). AQP-5, in contrast, was not associated to mitotic figures, but was predominantly expressed during late stages of SG morphogenesis. Our results highlight that AQPs are expressed from early stages of SG morphogenesis and exhibit complimentary expression patterns that may contribute to the morphogenesis of salivary glands.
- Published
- 2020
49. Balance Between Tooth Size and Tooth Number Is Controlled by Hyaluronan
- Author
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Jingjing Li, Esteban G. Contreras, Marcia Gaete, Abigail S. Tucker, Angélica Ubilla, María Constanza González-Ramírez, Anyeli Valencia, Jeremy B. Green, Andrés Wilson, and Natalia Sánchez
- Subjects
0301 basic medicine ,Molar ,Physiology ,organogenesis ,Cell ,lcsh:Physiology ,Extracellular matrix ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,stomatognathic system ,cell orientation ,Physiology (medical) ,Hyaluronic acid ,medicine ,Receptor ,Original Research ,lcsh:QP1-981 ,Chemistry ,Cell growth ,Regeneration (biology) ,Mesenchymal stem cell ,molar development ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,successional tooth development ,activator-inhibitor - Abstract
While the function of proteins and genes has been widely studied during vertebrate development, relatively little work has addressed the role of carbohydrates. Hyaluronan (HA), also known as hyaluronic acid, is an abundant carbohydrate in embryonic tissues and is the main structural component of the extracellular matrix of epithelial and mesenchymal cells. HA is able to absorb large quantities of water and can signal by binding to cell-surface receptors. During organ development and regeneration, HA has been shown to regulate cell proliferation, cell shape, and migration. Here, we have investigated the function of HA during molar tooth development in mice, in which, similar to humans, new molars sequentially bud off from a pre-existing molar. Using an ex vivo approach, we found that inhibiting HA synthesis in culture leads to a significant increase in proliferation and subsequent size of the developing molar, while the formation of sequential molars was inhibited. By cell shape analysis, we observed that inhibition of HA synthesis caused an elongation and reorientation of the major cell axes, indicating that disruption to cellular orientation and shape may underlie the observed phenotype. Lineage tracing demonstrated the retention of cells in the developing first molar (M1) at the expense of the generation of a second molar (M2). Our results highlight a novel role for HA in controlling proliferation, cell orientation, and migration in the developing tooth, impacting cellular decisions regarding tooth size and number.
- Published
- 2020
50. Development of the Vestibular Lamina in Human Embryos: Morphogenesis and Vestibule Formation
- Author
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Abigail S. Tucker, Maria Hovorakova, Tathyane Harumi Nakajima Teshima, and Tengyang Qiu
- Subjects
0301 basic medicine ,Vestibular lamina ,Physiology ,Morphogenesis ,Biology ,lcsh:Physiology ,03 medical and health sciences ,0302 clinical medicine ,stomatognathic system ,Physiology (medical) ,medicine ,Supernumerary ,Oral mucosa ,keratin ,Original Research ,lcsh:QP1-981 ,oral mucosa ,apoptosis ,Anatomy ,Cheek ,Dental lamina ,epithelial differentiation ,stomatognathic diseases ,030104 developmental biology ,medicine.anatomical_structure ,human development ,Vestibule ,dental pathologies ,030217 neurology & neurosurgery ,Filaggrin - Abstract
The vestibular lamina (VL) is a transient developmental structure that forms the lip furrow, creating a gap between the lips/cheeks and teeth (oral vestibule). Surprisingly, little is known about the development of the VL and its relationship to the adjacent dental lamina (DL), which forms the teeth. In some congenital disorders, such as Ellis-van Creveld (EVC) syndrome, development of the VL is disrupted and multiple supernumerary frenula form, physically linking the lips and teeth. Here, we assess the normal development of the VL in human embryos from 6.5 (CS19) to 13 weeks of development, showing the close relationship between the VL and DL, from initiation to differentiation. In the anterior lower region, the two structures arise from the same epithelial thickening. The VL then undergoes complex morphogenetic changes during development, forming a branched structure that separates to create the vestibule. Changing expression of keratins highlight the differentiation patterns in the VL, with fissure formation linked to the onset of filaggrin. Apoptosis is involved in removal of the central portion of the VL to create a broad furrow between the future cheek and gum. This research forms an essential base to further explore developmental defects in this part of the oral cavity.
- Published
- 2020
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