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Fibroblast growth factor signaling and basement membrane assembly are connected during epithelial morphogenesis of the embryoid body

Li, Xiaofeng; Chen, Yali; Schéele, Susanne LU ; Arman, Esther; Haffner-Krausz, Rebecca; Ekblom, Peter LU and Lonai, Peter (2001) In Journal of Cell Biology 153(4). p.811-822
Abstract
Fibroblast growth factors and receptors are intimately connected to the extracellular matrix by their affinity to heparan sulfate proteoglycans. They mediate multiple processes during embryonic development and adult life. In this study, embryonic stem cell-derived embryoid bodies were used to model fibroblast growth factor signaling during early epithelial morphogenesis. To avoid redundancy caused by multiple receptors, we employed a dominant negative mutation of Fgfr2. Mutant-derived embryoid bodies failed to form endoderm, ectoderm, and basement membrane and did not cavitate. However, in mixed cultures they displayed complete differentiation induced by extracellular products of the normal cell. Evidence will be presented here that at... (More)
Fibroblast growth factors and receptors are intimately connected to the extracellular matrix by their affinity to heparan sulfate proteoglycans. They mediate multiple processes during embryonic development and adult life. In this study, embryonic stem cell-derived embryoid bodies were used to model fibroblast growth factor signaling during early epithelial morphogenesis. To avoid redundancy caused by multiple receptors, we employed a dominant negative mutation of Fgfr2. Mutant-derived embryoid bodies failed to form endoderm, ectoderm, and basement membrane and did not cavitate. However, in mixed cultures they displayed complete differentiation induced by extracellular products of the normal cell. Evidence will be presented here that at least one of these products is the basement membrane or factors connected to it. It will be shown that in the mutant, collagen IV and laminin-1 synthesis is coordinately suppressed. We will demonstrate that the basement membrane is required for embryoid body differentiation by rescuing columnar ectoderm differentiation and cavitation in the mutant by externally added basement membrane proteins. This treatment induced transcription of Eomesodermin, an early developmental gene, suggesting that purified basement membrane proteins can activate inherent developmental programs. Our results provide a new paradigm for the role of fibroblast growth factor signaling in basement membrane formation and epithelial differentiation. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
epithelial differentiation, embryoid bodies, early development, basement membrane, FGF signaling
in
Journal of Cell Biology
volume
153
issue
4
pages
811 - 822
publisher
Rockefeller University Press
external identifiers
  • pmid:11352941
  • scopus:0035858870
ISSN
0021-9525
DOI
10.1083/jcb.153.4.811
language
English
LU publication?
yes
id
346bfaa5-459b-43b9-ae90-9eef01e871bc (old id 1121244)
date added to LUP
2008-07-03 11:09:07
date last changed
2018-01-07 05:59:30
@article{346bfaa5-459b-43b9-ae90-9eef01e871bc,
  abstract     = {Fibroblast growth factors and receptors are intimately connected to the extracellular matrix by their affinity to heparan sulfate proteoglycans. They mediate multiple processes during embryonic development and adult life. In this study, embryonic stem cell-derived embryoid bodies were used to model fibroblast growth factor signaling during early epithelial morphogenesis. To avoid redundancy caused by multiple receptors, we employed a dominant negative mutation of Fgfr2. Mutant-derived embryoid bodies failed to form endoderm, ectoderm, and basement membrane and did not cavitate. However, in mixed cultures they displayed complete differentiation induced by extracellular products of the normal cell. Evidence will be presented here that at least one of these products is the basement membrane or factors connected to it. It will be shown that in the mutant, collagen IV and laminin-1 synthesis is coordinately suppressed. We will demonstrate that the basement membrane is required for embryoid body differentiation by rescuing columnar ectoderm differentiation and cavitation in the mutant by externally added basement membrane proteins. This treatment induced transcription of Eomesodermin, an early developmental gene, suggesting that purified basement membrane proteins can activate inherent developmental programs. Our results provide a new paradigm for the role of fibroblast growth factor signaling in basement membrane formation and epithelial differentiation.},
  author       = {Li, Xiaofeng and Chen, Yali and Schéele, Susanne and Arman, Esther and Haffner-Krausz, Rebecca and Ekblom, Peter and Lonai, Peter},
  issn         = {0021-9525},
  keyword      = {epithelial differentiation,embryoid bodies,early development,basement membrane,FGF signaling},
  language     = {eng},
  number       = {4},
  pages        = {811--822},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Cell Biology},
  title        = {Fibroblast growth factor signaling and basement membrane assembly are connected during epithelial morphogenesis of the embryoid body},
  url          = {http://dx.doi.org/10.1083/jcb.153.4.811},
  volume       = {153},
  year         = {2001},
}