Fibroblast growth factor signaling and basement membrane assembly are connected during epithelial morphogenesis of the embryoid body
(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:
https://lup.lub.lu.se/record/1121244
- author
- Li, Xiaofeng ; Chen, Yali ; Schéele, Susanne LU ; Arman, Esther ; Haffner-Krausz, Rebecca ; Ekblom, Peter LU and Lonai, Peter
- organization
- publishing date
- 2001
- 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
- 2016-04-01 12:15:50
- date last changed
- 2022-06-23 20:58:52
@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}},
keywords = {{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}},
doi = {{10.1083/jcb.153.4.811}},
volume = {{153}},
year = {{2001}},
}