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

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-de...

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Bibliographic Details
Published in:Genes & development 2008-07, Vol.22 (13), p.1828-1837
Main Authors: Lagha, Mounia, Kormish, Jay D, Rocancourt, Didier, Manceau, Marie, Epstein, Jonathan A, Zaret, Kenneth S, Relaix, Frédéric, Buckingham, Margaret E
Format: Article
Language:English
Subjects:
3' Flanking Region
Adaptor Proteins, Signal Transducing
Amino Acid Sequence
Animals
Cell Differentiation
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
Fibroblast Growth Factors - physiology
Life Sciences
Membrane Proteins - metabolism
Mice
Molecular Sequence Data
Muscle Development
Myoblasts - cytology
Myoblasts - metabolism
Paired Box Transcription Factors - physiology
PAX3 Transcription Factor
Phosphoproteins - metabolism
Receptor, Fibroblast Growth Factor, Type 4 - metabolism
Research Paper
Response Elements
Signal Transduction
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Summary: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.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.477908