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Synergistic interaction between the fibroblast growth factor and bone morphogenetic protein signaling pathways in lens cells

Fibroblast growth factors (FGFs) play a central role in two processes essential for lens transparency—fiber cell differentiation and gap junction–mediated intercellular communication (GJIC). Using serum-free primary cultures of chick lens epithelial cells (DCDMLs), we investigated how the FGF and bo...

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Detalles Bibliográficos
Autores principales: Boswell, Bruce A., Musil, Linda S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571308/
https://www.ncbi.nlm.nih.gov/pubmed/25947138
http://dx.doi.org/10.1091/mbc.E15-02-0117
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author Boswell, Bruce A.
Musil, Linda S.
author_facet Boswell, Bruce A.
Musil, Linda S.
author_sort Boswell, Bruce A.
collection PubMed
description Fibroblast growth factors (FGFs) play a central role in two processes essential for lens transparency—fiber cell differentiation and gap junction–mediated intercellular communication (GJIC). Using serum-free primary cultures of chick lens epithelial cells (DCDMLs), we investigated how the FGF and bone morphogenetic protein (BMP) signaling pathways positively cooperate to regulate lens development and function. We found that culturing DCDMLs for 6 d with the BMP blocker noggin inhibits the canonical FGF-to-ERK pathway upstream of FRS2 activation and also prevents FGF from stimulating FRS2- and ERK-independent gene expression, indicating that BMP signaling is required at the level of FGF receptors. Other experiments revealed a second type of BMP/FGF interaction by which FGF promotes expression of BMP target genes as well as of BMP4. Together these studies reveal a novel mode of cooperation between the FGF and BMP pathways in which BMP keeps lens cells in an optimally FGF-responsive state and, reciprocally, FGF enhances BMP-mediated gene expression. This interaction provides a mechanistic explanation for why disruption of either FGF or BMP signaling in the lens leads to defects in lens development and function.
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spelling pubmed-45713082015-09-29 Synergistic interaction between the fibroblast growth factor and bone morphogenetic protein signaling pathways in lens cells Boswell, Bruce A. Musil, Linda S. Mol Biol Cell Articles Fibroblast growth factors (FGFs) play a central role in two processes essential for lens transparency—fiber cell differentiation and gap junction–mediated intercellular communication (GJIC). Using serum-free primary cultures of chick lens epithelial cells (DCDMLs), we investigated how the FGF and bone morphogenetic protein (BMP) signaling pathways positively cooperate to regulate lens development and function. We found that culturing DCDMLs for 6 d with the BMP blocker noggin inhibits the canonical FGF-to-ERK pathway upstream of FRS2 activation and also prevents FGF from stimulating FRS2- and ERK-independent gene expression, indicating that BMP signaling is required at the level of FGF receptors. Other experiments revealed a second type of BMP/FGF interaction by which FGF promotes expression of BMP target genes as well as of BMP4. Together these studies reveal a novel mode of cooperation between the FGF and BMP pathways in which BMP keeps lens cells in an optimally FGF-responsive state and, reciprocally, FGF enhances BMP-mediated gene expression. This interaction provides a mechanistic explanation for why disruption of either FGF or BMP signaling in the lens leads to defects in lens development and function. The American Society for Cell Biology 2015-07-01 /pmc/articles/PMC4571308/ /pubmed/25947138 http://dx.doi.org/10.1091/mbc.E15-02-0117 Text en © 2015 Boswell and Musil. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Boswell, Bruce A.
Musil, Linda S.
Synergistic interaction between the fibroblast growth factor and bone morphogenetic protein signaling pathways in lens cells
title Synergistic interaction between the fibroblast growth factor and bone morphogenetic protein signaling pathways in lens cells
title_full Synergistic interaction between the fibroblast growth factor and bone morphogenetic protein signaling pathways in lens cells
title_fullStr Synergistic interaction between the fibroblast growth factor and bone morphogenetic protein signaling pathways in lens cells
title_full_unstemmed Synergistic interaction between the fibroblast growth factor and bone morphogenetic protein signaling pathways in lens cells
title_short Synergistic interaction between the fibroblast growth factor and bone morphogenetic protein signaling pathways in lens cells
title_sort synergistic interaction between the fibroblast growth factor and bone morphogenetic protein signaling pathways in lens cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571308/
https://www.ncbi.nlm.nih.gov/pubmed/25947138
http://dx.doi.org/10.1091/mbc.E15-02-0117
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