Essential role of glycosaminoglycans in Fgf signaling during mouse gastrulation Journal Article


Authors: Garcia-Garcia, M. J.; Anderson, K. V.
Article Title: Essential role of glycosaminoglycans in Fgf signaling during mouse gastrulation
Abstract: In vitro studies have suggested that proteoglycans facilitate signaling by mammalian growth factors, but genetic evidence supporting this role has been lacking. Here, we characterize the ENU-induced mutation lazy mesoderm (lzme), which disrupts the single mouse gene encoding UDP-glucose dehydrogenase (Ugdh), an enzyme required for the synthesis of the glycosaminoglycan (GAG) side chains of proteoglycans. lzme mutants arrest during gastrulation with defects in migration of mesoderm and endoderm, a phenotype similar to that of mutants in the fibroblast growth factor (Fgf) pathway. Analysis of the expression of molecular markers indicates that Fgf signaling is blocked in lzme mutant embryos. In contrast, signaling by the growth factors Nodal and Wnt3, which are also essential during mouse gastrulation, appears to be normal in lzme embryos. The results demonstrate that proteoglycans are required during mouse gastrulation specifically to promote Fgf signaling.
Keywords: signal transduction; controlled study; protein expression; gene mutation; mutation; nonhuman; proteins; mouse; mammalia; animals; mice; transforming growth factor beta; embryo; in vitro study; mice, transgenic; molecular marker; protein synthesis; mammal; fibroblast; cell movement; wnt proteins; mesoderm; genetic code; fibroblast growth factor; fibroblast growth factors; endoderm; mutant; gastrulation; gastrula; proteoglycan; glycosaminoglycan; male; female; priority journal; article; glycosaminoglycans; uridine diphosphate glucose dehydrogenase
Journal Title: Cell
Volume: 114
Issue: 6
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2003-09-19
Start Page: 727
End Page: 737
Language: English
DOI: 10.1016/s0092-8674(03)00715-3
PUBMED: 14505572
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
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  1. Kathryn Anderson
    148 Anderson