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FGF/FGFR Signaling Coordinates Skull Development by Modulating Magnitude of Morphological Integration: Evidence from Apert Syndrome Mouse Models

The fibroblast growth factor and receptor system (FGF/FGFR) mediates cell communication and pattern formation in many tissue types (e.g., osseous, nervous, vascular). In those craniosynostosis syndromes caused by FGFR1-3 mutations, alteration of signaling in the FGF/FGFR system leads to dysmorpholog...

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Autores principales: Martínez-Abadías, Neus, Heuzé, Yann, Wang, Yingli, Jabs, Ethylin Wang, Aldridge, Kristina, Richtsmeier, Joan T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203899/
https://www.ncbi.nlm.nih.gov/pubmed/22053191
http://dx.doi.org/10.1371/journal.pone.0026425
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author Martínez-Abadías, Neus
Heuzé, Yann
Wang, Yingli
Jabs, Ethylin Wang
Aldridge, Kristina
Richtsmeier, Joan T.
author_facet Martínez-Abadías, Neus
Heuzé, Yann
Wang, Yingli
Jabs, Ethylin Wang
Aldridge, Kristina
Richtsmeier, Joan T.
author_sort Martínez-Abadías, Neus
collection PubMed
description The fibroblast growth factor and receptor system (FGF/FGFR) mediates cell communication and pattern formation in many tissue types (e.g., osseous, nervous, vascular). In those craniosynostosis syndromes caused by FGFR1-3 mutations, alteration of signaling in the FGF/FGFR system leads to dysmorphology of the skull, brain and limbs, among other organs. Since this molecular pathway is widely expressed throughout head development, we explore whether and how two specific mutations on Fgfr2 causing Apert syndrome in humans affect the pattern and level of integration between the facial skeleton and the neurocranium using inbred Apert syndrome mouse models Fgfr2(+/S252W) and Fgfr2(+/P253R) and their non-mutant littermates at P0. Skull morphological integration (MI), which can reflect developmental interactions among traits by measuring the intensity of statistical associations among them, was assessed using data from microCT images of the skull of Apert syndrome mouse models and 3D geometric morphometric methods. Our results show that mutant Apert syndrome mice share the general pattern of MI with their non-mutant littermates, but the magnitude of integration between and within the facial skeleton and the neurocranium is increased, especially in Fgfr2(+/S252W) mice. This indicates that although Fgfr2 mutations do not disrupt skull MI, FGF/FGFR signaling is a covariance-generating process in skull development that acts as a global factor modulating the intensity of MI. As this pathway evolved early in vertebrate evolution, it may have played a significant role in establishing the patterns of skull MI and coordinating proper skull development.
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spelling pubmed-32038992011-11-03 FGF/FGFR Signaling Coordinates Skull Development by Modulating Magnitude of Morphological Integration: Evidence from Apert Syndrome Mouse Models Martínez-Abadías, Neus Heuzé, Yann Wang, Yingli Jabs, Ethylin Wang Aldridge, Kristina Richtsmeier, Joan T. PLoS One Research Article The fibroblast growth factor and receptor system (FGF/FGFR) mediates cell communication and pattern formation in many tissue types (e.g., osseous, nervous, vascular). In those craniosynostosis syndromes caused by FGFR1-3 mutations, alteration of signaling in the FGF/FGFR system leads to dysmorphology of the skull, brain and limbs, among other organs. Since this molecular pathway is widely expressed throughout head development, we explore whether and how two specific mutations on Fgfr2 causing Apert syndrome in humans affect the pattern and level of integration between the facial skeleton and the neurocranium using inbred Apert syndrome mouse models Fgfr2(+/S252W) and Fgfr2(+/P253R) and their non-mutant littermates at P0. Skull morphological integration (MI), which can reflect developmental interactions among traits by measuring the intensity of statistical associations among them, was assessed using data from microCT images of the skull of Apert syndrome mouse models and 3D geometric morphometric methods. Our results show that mutant Apert syndrome mice share the general pattern of MI with their non-mutant littermates, but the magnitude of integration between and within the facial skeleton and the neurocranium is increased, especially in Fgfr2(+/S252W) mice. This indicates that although Fgfr2 mutations do not disrupt skull MI, FGF/FGFR signaling is a covariance-generating process in skull development that acts as a global factor modulating the intensity of MI. As this pathway evolved early in vertebrate evolution, it may have played a significant role in establishing the patterns of skull MI and coordinating proper skull development. Public Library of Science 2011-10-28 /pmc/articles/PMC3203899/ /pubmed/22053191 http://dx.doi.org/10.1371/journal.pone.0026425 Text en Martínez-Abadías et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Martínez-Abadías, Neus
Heuzé, Yann
Wang, Yingli
Jabs, Ethylin Wang
Aldridge, Kristina
Richtsmeier, Joan T.
FGF/FGFR Signaling Coordinates Skull Development by Modulating Magnitude of Morphological Integration: Evidence from Apert Syndrome Mouse Models
title FGF/FGFR Signaling Coordinates Skull Development by Modulating Magnitude of Morphological Integration: Evidence from Apert Syndrome Mouse Models
title_full FGF/FGFR Signaling Coordinates Skull Development by Modulating Magnitude of Morphological Integration: Evidence from Apert Syndrome Mouse Models
title_fullStr FGF/FGFR Signaling Coordinates Skull Development by Modulating Magnitude of Morphological Integration: Evidence from Apert Syndrome Mouse Models
title_full_unstemmed FGF/FGFR Signaling Coordinates Skull Development by Modulating Magnitude of Morphological Integration: Evidence from Apert Syndrome Mouse Models
title_short FGF/FGFR Signaling Coordinates Skull Development by Modulating Magnitude of Morphological Integration: Evidence from Apert Syndrome Mouse Models
title_sort fgf/fgfr signaling coordinates skull development by modulating magnitude of morphological integration: evidence from apert syndrome mouse models
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203899/
https://www.ncbi.nlm.nih.gov/pubmed/22053191
http://dx.doi.org/10.1371/journal.pone.0026425
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