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Session Schedule & Abstracts
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|Friday 1st July, 2016|
|Moderator(s): J. Richman, C. M. Holliday, & J. Abramyan|
PLT1-1 9:30 am Molecular patterning of the hard palate during mammalian palatogenesis. YE W*, Tulane University; Huang Z, Tulane University; Fujian Normal University; Chen Y, Tulane University email@example.com |
Abstract: The mammalian palate is anatomically divided into the anterior hard palate and the posterior soft palate. However, how the anterior hard palate is patterned and how the palatal osteogenesis is controlled remain unknown. It was recently demonstrated that in the developing branchial arches, the TALE superclass homeodomain proteins particularly Meis proteins set up a ground state that is common to all the arches and their derivatives whereas Hox transcription factors act as tissue-specific cofactor to specify the arch identity. However, this raises a fundamental question as what factors interact with Meis to specify and pattern the Hox-free first arch and its derivatives including the palate. The homeobox gene Shox2 is expressed specifically in the anterior palatal mesenchyme, overlapping with the future bony hard palate domain. We have shown previously that Shox2 mutation leads to not only anterior palate clefting, but most intriguingly, to significantly reduced bone formation in the hard palate. Together with the loss of the stypolod in Shox2-/- limb, there is an essential role for Shox2 in organ patterning and skeletogenesis. Our recent studies present evidence that inactivation of Shox2 leads to premature/ectopic expression of Runx2 in Shox2-expressing palatal mesenchymal cells. Our RNA-Seq studies on Shox2+ cells from E13 palatal shelves and limbs demonstrate a genome-wide elevated expression of osteogenic genes in the absence of Shox2, consistent with our results that Shox2 overexpression in CNC lineage cells causes cleft and inhibits osteogenesis. Moreover, Shox2 ChIP-Seq on the developing palate and limb reveals genome-wide preferential occupation of Shox2 on the responsive cis-regulatory elements of these genes bound by Hox and Meis proteins. These results suggest that in the Hox-free developing palate, Shox2 interacts with Meis to pattern the hard palate and regulates osteogenesis by antagonizing the transcription output of Meis proteins to prevent premature osteogenic differentiation. (supported by NIH grants R01 DE14044 and R01DE17792).
PLT1-2 10:00 am Differing effects of Fgfr mutations on palate morphology in non-cleft mouse models. Martinez-Abadias Neus*, Center for Genomic Regulation; Motch Perrine Susan, Pennsylvania State University; Melkonian Freya, Universitat de Barcelona; Pankratz Talia, Pennsylvania State University; Rhodes Katie, Pennsylvania State University; Wang Yingli, Icahn School of Medicine at Mount Sinai; Zhou Xueyan, Icahn School of Medicine at Mount Sinai; Wang Jabs Ethyli, Icahn School of Medicine at Mount Sinai; Richtsmeier Joan, Pennsylvania State University firstname.lastname@example.org |
Abstract: FGFR1-3 -related craniosynostosis syndromes are autosomal congenital disorders that involve craniofacial, neural and other malformations caused by mutations in the FGF/FGFR signaling pathway. Even though the syndromes present overlapping phenotypes and mutations can reside on neighboring amino acids of the same gene, the craniofacial phenotype shows marked variation within and between syndromes. Focusing on palate development, our goal is to pinpoint differences in the emergence and severity of palatal dysmorphologies between some of the most prevalent craniosynostosis syndromes using murine models for Apert (Fgfr2+/S252W and Fgfr2+/P253R), Crouzon (Fgfr2+/C342Y) and Muenke (Fgfr3+/P244R) syndromes at two different developmental times (embryonic day 17.5 and day of birth P0). Results based on palatal suture patency and comparative 3D shape analysis of landmark-based data recorded on high resolution micro CT scans of mutant and non-mutant littermates confirmed that across these mutation groups, the posterior aspect is the most affected region of the palate. However, the Apert Fgrf2 S252W mutation caused earlier onset (before E17.5) and resulted in the most severe palate dysmorphology by P0. The remaining mutations are associated with later onset (between E17.5 and birth) and less severe palatal defects. The least disruptive mutation was the Muenke Fgfr3 P244R mutation, which induced palatal dysmorphologies only when present in two copies (Fgfr3P244R/P244R). We conclude that the onset time, gene dosage and spatio-temporal expression patterns of the Fgfrs affected by these mutations may explain the phenotypic dissimilarities between FGFR1-3 related craniosynostosis syndromes. Further experimental analyses guided by our morphometric results may reveal the mechanisms leading to the most severe palatal anomalies in craniosynostosis syndromes. Grant support: NIH/NIDCR (R01 DE018500, 3R01 DE018500-02S1, R01 DE022988, P01HD078233), FP7-PEOPLE-2012-IIF 327382, SEV-2012-0208.
PLT1-3 10:15 am An open and shut case; Variation in morphogenesis of the secondary palate in amniotes. Richman JM*, University of British Columbia; Higashihori N, Tokyo Medical and Dental School; Abramyan J, University of British Columbia email@example.com |
Abstract: The secondary palate forms the roof of the oral cavity, posterior to the primary palate. The bones supporting the palate in mammalian line of amniotes consist of the palatine process of the maxillary bone and the palatine bone whereas in the reptilian line, the pterygoid also makes an important contribution. The mammalian amniotes have an unbroken evolutionary record of intact palates. Furthermore, the mammalian secondary palate includes the muscular soft palate which is not preserved in the fossil record. In contrast, in the reptilian line, squamates and aves have open secondary palates but lack an equivalent to the soft palate. Many studies in the mouse have documented anterior-posterior differences in gene expression that correlate with the putative border of the hard and soft palate. We hypothesized that in the avian embryo, such positionally restricted patterns would not exist. In the chicken, the medial surfaces of the maxillary prominences grow outward to form the palatal shelves starting at stage 29, by stage 33 the palate has fully formed and ossification begins at stage 34. The posteriorly restricted genes examined included BARX1, TBX22, BMP4, PAX9 and MN1. We also looked at SHOX2 and MSX1 which are anteriorly expressed in mice. In the chicken the majority of genes varied in their expression patterns compared to the mouse. PAX9 is ubiquitously expressed while MSX1 is absent from the anterior palatal shelves. Interestingly, TBX22 is expressed medially throughout the palatal shelves at stage 31 and 32 but is downregulated posteriorly at stage 33. Only one gene, BARX1, is correlated with the posteriorly positioned pterygoid bones. Therefore the molecular patterning in the bird does not follow the anterior-posterior regionalization seen in the mouse. We uncovered a set of genes with conserved expression in the palates of birds and mammals however our detailed examination suggests the regulatory regions may be slightly different.
PLT1-4 10:30 am Mechanisms of crocodilian palate formation. Abramyan J*, University of British Columbia; Richman JM, University of British Columbia firstname.lastname@example.org |
Abstract: Amniote embryos develop a connection between the embryonic mouth (stomodeum) and the nasal cavities. Subsequently, a secondary palate forms in most lineages. In snakes, lizards and birds, palatal shelves bud out from the maxillary prominences but do not fuse, leaving a natural cleft. In mammals and crocodilians, the secondary palate completely separates the oral and nasal cavities. However, the details of crocodilian secondary palate formation are unclear. Here we describe the ontogeny of the secondary palate in alligator embryos using histology, immunohistochemistry and 3D reconstruction. We found that at stage 14 and 15 (Ferguson staging), the choanae open into the oral cavity unobstructed, although slight thickening of the medial sides of the maxillary prominences are visible posterior to the choanae. The midline mesenchyme inferior to the nasal septal cartilage also projects into the stomodeum. At stages 16 through 17, the medial sides of the maxillary prominences become enlarged so that by stage 17, fusion initiates between the medial maxillary prominences and nasal epithelium. At stages 18-19, the zone of fusion between the palatal shelves extends posteriorly, retaining connection to the nasal septum and furthermore, beginning to contact each other directly. Anti-cytokeratin staining confirms the presence of epithelial contact between the maxillary prominences over a limited distance (14-21 microns), indicating an extremely short period of epithelial seam retention. In mammals, palatal shelves develop vertically and then reorient horizontally to make extensive epithelial contact in the midline. The medial edge epithelium persists throughout the length of the palate, gradually degrading and being replaced by mesenchyme. The crocodilian maxillary prominences enlarge medially, make anterior contact with the premaxilla and the nasal septum first, and then gradually merge down the midline in a posterior direction to form a complete, flat secondary palate.
PLT1-5 10:45 am Morphology and development of secondary palate in chameleon. Hampl M*, Laboratory of Molecular Morphogenesis, Institute of Animal Physiology and Genetics, v.v.i., AS; CR; Department of Animal Physiology and Immunology, Faculty of Science, Masaryk University, Brno, Czech Republic; Dosedelova H, Laboratory of Molecular Morphogenesis, Institute of Animal Physiology and Genetics, v.v.i., AS; Department of Anatomy, Histology, and Embryology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic; Zahradnicek O, Department of Teratology, Institute of Experimental Medicine, v.v.i. Academy of Sciences of the Czech Republic, Prague, Czech Republic; Pyszko M, Department of Anatomy, Histology, and Embryology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic; Zikmund T, Materials Characterization and Advanced Coatings Research Group, CEITEC BUT, Brno, Czech Republic; Buchtova M, Laboratory of Molecular Morphogenesis, Institute of Animal Physiology and Genetics, v.v.i., AS CR; Department of Animal Physiology and Immunology, Faculty of Science, Masaryk University, Brno, Czech Republic email@example.com |
Abstract: In some groups of reptiles such as turtles, crocodiles and lizards, various degree of secondary palates have developed. In chameleons, the secondary palate is supported by palatine processes of the premaxilla and maxilla as well as by the palatal and pterygoid bones. The vomer is situated medially. In some post-hatching individuals, we observed open palates while in others there was partial fusion of palatal shelves in the midline. Here, we focus on the analysis of developmental processes underlying secondary palate formation and their differences in comparison to mammals. During pre-hatching development, lateral palatal shelves in chameleons grow dorso-medially toward each other, covering the interorbital septum and choanae. The palate was open rostrally and caudally while closer approximation of the shelves was found in the centre. . The growing medial edge of palatal shelves was covered by cylindrical epithelial cells containing apical nuclei.. On the other hand, epithelial cells of the nasal and the oral cavity were flattened. Immunohistochemical analysis of PCNA revealed massive proliferation in multilayered oral epithelium as well as in the medial part of the mesenchyme. To experimentally affect the palate development, we dissected palatal shelves from embryos in the middle of pre-hatching development. We did not observed any sign of fusion when palatal shelves were cultured next to each other. On the other hand, the full fusion was found in cultures treated with TGFbeta added to the culture medium. Our preliminary results revealed that fusion of the chameleon palate can be enhanced by growth factors. Future work will uncover the cellular and molecular processes responsible for secondary palate fusion in chameleons. The research was supported by Grant Agency of Czech Republic (14-37368G).
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