Transient Inhibition of FGFR2b-ligands signaling leads to irreversible loss of cellular β-catenin organization and signaling in AER during mouse limb development.

The vertebrate limbs develop through coordinated series of inductive, growth and patterning events. Fibroblast Growth Factor receptor 2b (FGFR2b) signaling controls the induction of the Apical Ectodermal Ridge (AER) but its putative roles in limb outgrowth and patterning, as well as in AER morpholog...

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Autores principales:	Soula Danopoulos, Sara Parsa, Denise Al Alam, Reza Tabatabai, Sheryl Baptista, Caterina Tiozzo, Gianni Carraro, Matthew Wheeler, Guillermo Barreto, Thomas Braun, Xiaokun Li, Mohammad K Hajihosseini, Saverio Bellusci
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/35cf2527a6a447d69017a5346522f76f
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spelling	oai:doaj.org-article:35cf2527a6a447d69017a5346522f76f2021-11-18T08:50:03ZTransient Inhibition of FGFR2b-ligands signaling leads to irreversible loss of cellular β-catenin organization and signaling in AER during mouse limb development.1932-620310.1371/journal.pone.0076248https://doaj.org/article/35cf2527a6a447d69017a5346522f76f2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24167544/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The vertebrate limbs develop through coordinated series of inductive, growth and patterning events. Fibroblast Growth Factor receptor 2b (FGFR2b) signaling controls the induction of the Apical Ectodermal Ridge (AER) but its putative roles in limb outgrowth and patterning, as well as in AER morphology and cell behavior have remained unclear. We have investigated these roles through graded and reversible expression of soluble dominant-negative FGFR2b molecules at various times during mouse limb development, using a doxycycline/transactivator/tet(O)-responsive system. Transient attenuation (≤ 24 hours) of FGFR2b-ligands signaling at E8.5, prior to limb bud induction, leads mostly to the loss or truncation of proximal skeletal elements with less severe impact on distal elements. Attenuation from E9.5 onwards, however, has an irreversible effect on the stability of the AER, resulting in a progressive loss of distal limb skeletal elements. The primary consequences of FGFR2b-ligands attenuation is a transient loss of cell adhesion and down-regulation of P63, β1-integrin and E-cadherin, and a permanent loss of cellular β-catenin organization and WNT signaling within the AER. Combined, these effects lead to the progressive transformation of the AER cells from pluristratified to squamous epithelial-like cells within 24 hours of doxycycline administration. These findings show that FGFR2b-ligands signaling has critical stage-specific roles in maintaining the AER during limb development.Soula DanopoulosSara ParsaDenise Al AlamReza TabatabaiSheryl BaptistaCaterina TiozzoGianni CarraroMatthew WheelerGuillermo BarretoThomas BraunXiaokun LiMohammad K HajihosseiniSaverio BellusciPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 10, p e76248 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Soula Danopoulos Sara Parsa Denise Al Alam Reza Tabatabai Sheryl Baptista Caterina Tiozzo Gianni Carraro Matthew Wheeler Guillermo Barreto Thomas Braun Xiaokun Li Mohammad K Hajihosseini Saverio Bellusci Transient Inhibition of FGFR2b-ligands signaling leads to irreversible loss of cellular β-catenin organization and signaling in AER during mouse limb development.
description	The vertebrate limbs develop through coordinated series of inductive, growth and patterning events. Fibroblast Growth Factor receptor 2b (FGFR2b) signaling controls the induction of the Apical Ectodermal Ridge (AER) but its putative roles in limb outgrowth and patterning, as well as in AER morphology and cell behavior have remained unclear. We have investigated these roles through graded and reversible expression of soluble dominant-negative FGFR2b molecules at various times during mouse limb development, using a doxycycline/transactivator/tet(O)-responsive system. Transient attenuation (≤ 24 hours) of FGFR2b-ligands signaling at E8.5, prior to limb bud induction, leads mostly to the loss or truncation of proximal skeletal elements with less severe impact on distal elements. Attenuation from E9.5 onwards, however, has an irreversible effect on the stability of the AER, resulting in a progressive loss of distal limb skeletal elements. The primary consequences of FGFR2b-ligands attenuation is a transient loss of cell adhesion and down-regulation of P63, β1-integrin and E-cadherin, and a permanent loss of cellular β-catenin organization and WNT signaling within the AER. Combined, these effects lead to the progressive transformation of the AER cells from pluristratified to squamous epithelial-like cells within 24 hours of doxycycline administration. These findings show that FGFR2b-ligands signaling has critical stage-specific roles in maintaining the AER during limb development.
format	article
author	Soula Danopoulos Sara Parsa Denise Al Alam Reza Tabatabai Sheryl Baptista Caterina Tiozzo Gianni Carraro Matthew Wheeler Guillermo Barreto Thomas Braun Xiaokun Li Mohammad K Hajihosseini Saverio Bellusci
author_facet	Soula Danopoulos Sara Parsa Denise Al Alam Reza Tabatabai Sheryl Baptista Caterina Tiozzo Gianni Carraro Matthew Wheeler Guillermo Barreto Thomas Braun Xiaokun Li Mohammad K Hajihosseini Saverio Bellusci
author_sort	Soula Danopoulos
title	Transient Inhibition of FGFR2b-ligands signaling leads to irreversible loss of cellular β-catenin organization and signaling in AER during mouse limb development.
title_short	Transient Inhibition of FGFR2b-ligands signaling leads to irreversible loss of cellular β-catenin organization and signaling in AER during mouse limb development.
title_full	Transient Inhibition of FGFR2b-ligands signaling leads to irreversible loss of cellular β-catenin organization and signaling in AER during mouse limb development.
title_fullStr	Transient Inhibition of FGFR2b-ligands signaling leads to irreversible loss of cellular β-catenin organization and signaling in AER during mouse limb development.
title_full_unstemmed	Transient Inhibition of FGFR2b-ligands signaling leads to irreversible loss of cellular β-catenin organization and signaling in AER during mouse limb development.
title_sort	transient inhibition of fgfr2b-ligands signaling leads to irreversible loss of cellular β-catenin organization and signaling in aer during mouse limb development.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/35cf2527a6a447d69017a5346522f76f
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Transient Inhibition of FGFR2b-ligands signaling leads to irreversible loss of cellular β-catenin organization and signaling in AER during mouse limb development.

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