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PMID: 18593883 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Pax3 regulation of FGF signaling affects the progression of embryonic progenitor cells into the myogenic program.

Genes & development ·Vol. 22 ·No. 13 ·2008-07-01 ·Pages 1828-37

Lagha M, Kormish JD, Rocancourt D, Manceau M, Epstein JA, Zaret KS, Relaix F, Buckingham ME

Abstract

Pax3/7-dependent stem cells play an essential role in skeletal muscle development. We now show that Fgfr4 lies genetically downstream from Pax3 and is a direct target. In chromatin immunoprecipitation (ChIP)-on-chip experiments, Pax3 binds to a sequence 3' of the Fgfr4 gene that directs Pax3-dependent expression at sites of myogenesis in transgenic mouse embryos. The activity of this regulatory element is also partially dependent on E-boxes, targets of the myogenic regulatory factors, which are expressed as progenitor cells enter the myogenic program. Other FGF signaling components, notably Sprouty1, are also regulated by Pax3. In vivo manipulation of Sprouty expression reveals that FGF signaling affects the balance between Pax-positive progenitor cells and committed myoblasts. These results provide new insight into the Pax-initiated regulatory network that modulates stem cell maintenance versus tissue differentiation.

MeSH Terms
3' Flanking Region Adaptor Proteins, Signal Transducing Amino Acid Sequence Animals Cell Differentiation Embryonic Stem Cells/cytology,metabolism Fibroblast Growth Factors/physiology Membrane Proteins/metabolism Mice Molecular Sequence Data Muscle Development Myoblasts/cytology,metabolism PAX3 Transcription Factor Paired Box Transcription Factors/physiology Phosphoproteins/metabolism Receptor, Fibroblast Growth Factor, Type 4/metabolism Response Elements Signal Transduction
Chemicals
Adaptor Proteins, Signal Transducing Membrane Proteins PAX3 Transcription Factor Paired Box Transcription Factors Phosphoproteins Spry1 protein, mouse Pax3 protein, mouse Fibroblast Growth Factors Fgfr4 protein, mouse Receptor, Fibroblast Growth Factor, Type 4
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Lagha Mounia
CNRS URA 2578, Department of Developmental Biology, Pasteur Institute, 75015 Paris, France.
Kormish Jay D
Rocancourt Didier
Manceau Marie
Epstein Jonathan A
Zaret Kenneth S
Relaix Frédéric
Buckingham Margaret E
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.477908
Published
2008-07-01
Pages
1828-37
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC2492669
Subset
IM
Grants
NCI NIH HHS · P30 CA006927 · United States
NIGMS NIH HHS · R37 GM036477 · United States
NCI NIH HHS · CA06927 · United States
NIGMS NIH HHS · R37GM36477 · United States
External Links
PubMed source DOI: 10.1101/gad.477908 PMC Full Text View journal details
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