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PMID: 11572986 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Evidence that the WNT-inducible growth arrest-specific gene 1 encodes an antagonist of sonic hedgehog signaling in the somite.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 98 ·No. 20 ·2001-09-25 ·Pages 11347-52

Lee CS, Buttitta L, Fan CM

Abstract

The dorsal-ventral polarity of the somite is controlled by antagonistic signals from the dorsal neural tube/surface ectoderm, mediated by WNTs, and from the ventral notochord, mediated by sonic hedgehog (SHH). Each factor can act over a distance greater than a somite diameter in vitro, suggesting they must limit each other's actions within their own patterning domains in vivo. We show here that the growth-arrest specific gene 1 (Gas1), which is expressed in the dorsal somite, is induced by WNTs and encodes a protein that can bind to SHH. Furthermore, ectopic expression of Gas1 in presomitic cells attenuates the response of these cells to SHH in vitro. Taken together, these data suggest that GAS1 functions to reduce the availability of active SHH within the dorsal somite.

MeSH Terms
Animals Body Patterning/physiology COS Cells Cell Cycle Proteins Chlorocebus aethiops Embryonic Induction/physiology GPI-Linked Proteins Gene Expression Regulation Gene Library Genes, Reporter Hedgehog Proteins Membrane Proteins/genetics,metabolism Mice Mutagenesis, Site-Directed Protein-Tyrosine Kinases/metabolism Proto-Oncogene Proteins/metabolism Recombinant Proteins/metabolism Signal Transduction Somites/physiology Trans-Activators/antagonists & inhibitors,physiology Transfection Wnt Proteins Zebrafish Proteins
Chemicals
Cell Cycle Proteins GAS1 protein, human GPI-Linked Proteins Gas1 protein, mouse Hedgehog Proteins Membrane Proteins Proto-Oncogene Proteins Recombinant Proteins SHH protein, human Trans-Activators Wnt Proteins Zebrafish Proteins Protein-Tyrosine Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lee C S
Department of Embryology, Carnegie Institution of Washington, 115 West University Parkway, Baltimore, MD 21210, USA.
Buttitta L
Fan C M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.201418298
Published
2001-09-25
Pages
11347-52
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC58732
Subset
IM
Grants
NICHD NIH HHS · R01HD/GM35596 · United States
External Links
PubMed source DOI: 10.1073/pnas.201418298 PMC Full Text View journal details
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