title: Six homeoproteins directly activate Myod expression in the gene regulatory networks that control early myogenesis.
abstract: In mammals, several genetic pathways have been characterized that govern engagement of multipotent embryonic progenitors into the myogenic program through the control of the key myogenic regulatory gene Myod. Here we demonstrate the involvement of Six homeoproteins. We first targeted into a Pax3 allele a sequence encoding a negative form of Six4 that binds DNA but cannot interact with essential Eya co-factors. The resulting embryos present hypoplasic skeletal muscles and impaired Myod activation in the trunk in the absence of Myf5/Mrf4. At the axial level, we further show that Myod is still expressed in compound Six1/Six4:Pax3 but not in Six1/Six4:Myf5 triple mutant embryos, demonstrating that Six1/4 participates in the Pax3-Myod genetic pathway. Myod expression and head myogenesis is preserved in Six1/Six4:Myf5 triple mutant embryos, illustrating that upstream regulators of Myod in different embryonic territories are distinct. We show that Myod regulatory regions are directly controlled by Six proteins and that, in the absence of Six1 and Six4, Six2 can compensate.
authors: UPMC Paris 06, UMR-S 787, Paris, France. frelaix@gmail.com
authors: Frédéric
authors: F
authors: Relaix
authors: Josiane
authors: J
authors: Demignon
authors: Christine
authors: C
authors: Laclef
authors: Julien
authors: J
authors: Pujol
authors: Marc
authors: M
authors: Santolini
authors: Claire
authors: C
authors: Niro
authors: Mounia
authors: M
authors: Lagha
authors: Didier
authors: D
authors: Rocancourt
authors: Margaret
authors: M
authors: Buckingham
authors: Pascal
authors: P
authors: Maire
mesh_terms: D000818:Animals; D053263:Gene Regulatory Networks; D018398:Homeodomain Proteins / Q000235:genetics; D024510:Muscle Development; D014157:Transcription Factors / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors
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