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From shape to cells: mouse models reveal mechanisms altering palate development in Apert syndrome
Apert syndrome is a congenital disorder characterized by severe skull malformations and caused by one of two missense mutations, S252W and P253R, on fibroblast growth factor receptor 2 (FGFR2). The molecular bases underlying differential Apert syndrome phenotypes are still poorly understood and it i...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Limited
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634659/ https://www.ncbi.nlm.nih.gov/pubmed/23519026 http://dx.doi.org/10.1242/dmm.010397 |
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author | Martínez-Abadías, Neus Holmes, Greg Pankratz, Talia Wang, Yingli Zhou, Xueyan Jabs, Ethylin Wang Richtsmeier, Joan T. |
author_facet | Martínez-Abadías, Neus Holmes, Greg Pankratz, Talia Wang, Yingli Zhou, Xueyan Jabs, Ethylin Wang Richtsmeier, Joan T. |
author_sort | Martínez-Abadías, Neus |
collection | PubMed |
description | Apert syndrome is a congenital disorder characterized by severe skull malformations and caused by one of two missense mutations, S252W and P253R, on fibroblast growth factor receptor 2 (FGFR2). The molecular bases underlying differential Apert syndrome phenotypes are still poorly understood and it is unclear why cleft palate is more frequent in patients carrying the S252W mutation. Taking advantage of Apert syndrome mouse models, we performed a novel combination of morphometric, histological and immunohistochemical analyses to precisely quantify distinct palatal phenotypes in Fgfr2(+/S252W) and Fgfr2(+/P253R) mice. We localized regions of differentially altered FGF signaling and assessed local cell patterns to establish a baseline for understanding the differential effects of these two Fgfr2 mutations. Palatal suture scoring and comparative 3D shape analysis from high resolution μCT images of 120 newborn mouse skulls showed that Fgfr2(+/S252W) mice display relatively more severe palate dysmorphologies, with contracted and more separated palatal shelves, a greater tendency to fuse the maxillary-palatine sutures and aberrant development of the inter-premaxillary suture. These palatal defects are associated with suture-specific patterns of abnormal cellular proliferation, differentiation and apoptosis. The posterior region of the developing palate emerges as a potential target for therapeutic strategies in clinical management of cleft palate in Apert syndrome patients. |
format | Online Article Text |
id | pubmed-3634659 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The Company of Biologists Limited |
record_format | MEDLINE/PubMed |
spelling | pubmed-36346592013-06-19 From shape to cells: mouse models reveal mechanisms altering palate development in Apert syndrome Martínez-Abadías, Neus Holmes, Greg Pankratz, Talia Wang, Yingli Zhou, Xueyan Jabs, Ethylin Wang Richtsmeier, Joan T. Dis Model Mech Research Article Apert syndrome is a congenital disorder characterized by severe skull malformations and caused by one of two missense mutations, S252W and P253R, on fibroblast growth factor receptor 2 (FGFR2). The molecular bases underlying differential Apert syndrome phenotypes are still poorly understood and it is unclear why cleft palate is more frequent in patients carrying the S252W mutation. Taking advantage of Apert syndrome mouse models, we performed a novel combination of morphometric, histological and immunohistochemical analyses to precisely quantify distinct palatal phenotypes in Fgfr2(+/S252W) and Fgfr2(+/P253R) mice. We localized regions of differentially altered FGF signaling and assessed local cell patterns to establish a baseline for understanding the differential effects of these two Fgfr2 mutations. Palatal suture scoring and comparative 3D shape analysis from high resolution μCT images of 120 newborn mouse skulls showed that Fgfr2(+/S252W) mice display relatively more severe palate dysmorphologies, with contracted and more separated palatal shelves, a greater tendency to fuse the maxillary-palatine sutures and aberrant development of the inter-premaxillary suture. These palatal defects are associated with suture-specific patterns of abnormal cellular proliferation, differentiation and apoptosis. The posterior region of the developing palate emerges as a potential target for therapeutic strategies in clinical management of cleft palate in Apert syndrome patients. The Company of Biologists Limited 2013-05 2013-03-08 /pmc/articles/PMC3634659/ /pubmed/23519026 http://dx.doi.org/10.1242/dmm.010397 Text en © 2013. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0), which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms. |
spellingShingle | Research Article Martínez-Abadías, Neus Holmes, Greg Pankratz, Talia Wang, Yingli Zhou, Xueyan Jabs, Ethylin Wang Richtsmeier, Joan T. From shape to cells: mouse models reveal mechanisms altering palate development in Apert syndrome |
title | From shape to cells: mouse models reveal mechanisms altering palate development in Apert syndrome |
title_full | From shape to cells: mouse models reveal mechanisms altering palate development in Apert syndrome |
title_fullStr | From shape to cells: mouse models reveal mechanisms altering palate development in Apert syndrome |
title_full_unstemmed | From shape to cells: mouse models reveal mechanisms altering palate development in Apert syndrome |
title_short | From shape to cells: mouse models reveal mechanisms altering palate development in Apert syndrome |
title_sort | from shape to cells: mouse models reveal mechanisms altering palate development in apert syndrome |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634659/ https://www.ncbi.nlm.nih.gov/pubmed/23519026 http://dx.doi.org/10.1242/dmm.010397 |
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