Résumé :
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Vertebrate craniofacial and trunk myogenesis are regulated by distinct genetic programs. Branchiomeric craniofacial muscles regulate jaw opening and closing, facial expression and laryngeal and pharyngeal function. These muscles correspond to the gill musculature of fish and originate not from the somites, source of trunk and limb muscles, but from pharyngeal mesoderm. Prior to skeletal muscle specification branchiomeric muscle progenitor cells share the genetic program of a population of adjacent myocardial progenitor cells termed the second heart field which give rise to the right ventricle and outflow tract of the heart (Grifone and Kelly, 2007, Trends Genet 23, 365-9). Tbx1, murine homologue of the major DiGeorge/del22q11.2 syndrome candidate gene TBX1, is required for robust specification of branchiomeric craniofacial muscles in pharyngeal mesoderm (Kelly et al, 2004, Hum Mol Genet 13, 289-40). Here we examine the properties of branchiomeric and somite-derived muscle development in Tbx1 mutant embryos. Using immunohistochemistry we demonstrate that the myogenic regulatory factors Myf5 and MyoD are first activated in Tbx1 and Isl1-positive cells within core arch mesoderm. Despite altered fiber-type distributions and pharyngeal muscle weakness in TBX1 haploinsufficient del22q11.2 syndrome patients, myosin heavy chain type II and type I fiber distributions are indistinguishable in Tbx1+/+ and Tbx1+/- adult masseter and pharyngeal constrictor muscles. Furthermore, type I fibers are distributed normally in hypoplastic branchiomeric muscles which form sporadically in Tbx1-/- embryos. These sporadic muscles contain Pax7 positive cells and primary myocytes isolated from Tbx1-/- muscles have indistinguishable proliferative and myogenic differentiation properties from wild-type muscles in culture. A subset of somite-derived muscles express Tbx1, including certain limb muscles. These muscles display normal patterning, growth, fiber-type distribution and maturation in the absence of Tbx1. Together, our results suggest that the major role of Tbx1 during skeletal muscle development is restricted to myogenic specification of branchiomeric muscles.
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