Résumé :
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Six1 and Six4 are homeoproteins of the Six/sine oculis family. These proteins are expressed continuously during muscle development: in the dermomyotomal hypaxial myogenic progenitors, they control Pax3 expression and myogenic progenitors fate; in the migrating myogenic progenitors, they control Myf5 and later on myogenin and differentiation of myoblasts; in the adult muscle fiber, they control the fast/glycolytic phenotype; and in the adult satellite cells, they control muscle regeneration. Using Six1KO, Six1Six4dKO, and Six1lox conditional KO mice we have characterized the networks of genes under the control of these homeoproteins in various developmental contexts, and determined the functions of Six homeoproteins in the muscle lineage. I will summarize our work showing that Six genes are master regulators of muscle genes expression. I will describe evidence supporting that i) Six genes are directly involved in driving muscle fiber-type heterogeneity during fetal development ii) these genes are directly involved in controlling fast-type specialization of the adult myofiber and iii) these genes regulate the homeostasis of the satellite cells pool during regeneration.
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