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-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.
Lagha
Mounia
M
CNRS URA 2578, Department of Developmental Biology, Pasteur Institute, 75015 Paris, France.
Kormish
Jay D
JD
Rocancourt
Didier
D
Manceau
Marie
M
Epstein
Jonathan A
JA
Zaret
Kenneth S
KS
Relaix
Frédéric
F
Buckingham
Margaret E
ME
D024509:3' Flanking Region; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D024510:Muscle Development; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000378:metabolism; D020218:Response Elements; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D010750:Phosphoproteins; C425468:Spry1 protein, mouse; C068686:Pax3 protein, mouse; D005346:Fibroblast Growth Factors; C496372:Fgfr4 protein, mouse; D051499:Receptor, Fibroblast Growth Factor, Type 4