title: Semaphorin 3A promotes activation of Pax7, Myf5, and MyoD through inhibition of emerin expression in activated satellite cells.
abstract: We previously showed that Semaphorin 3A (Sema3A) expression was induced when quiescent muscle satellite cells were stimulated by hepatocyte growth factor and became activated satellite cells (ASCs). However, how Sema3A regulates genes in the early phase of ASCs remains unclear. In this study, we investigated whether Sema3A signaling can regulate the early phase of ASCs, an important satellite cell stage for postnatal growth, repair, and maintenance of skeletal muscle. We showed that expression of the myogenic proliferation regulatory factors Pax7 and Myf5 was decreased in myoblasts transfected with Sema3A siRNA. These cells failed to activate expression MyoD, another myogenic proliferation regulatory factor, during differentiation. Interestingly, some of the Sema3A-depleted cells did not express Pax7 and MyoD and had enlarged nuclei and very large cytoplasmic areas. We also observed that Pax7 and Myf5 expression was increased in Myc-Sema3A overexpressing myoblasts. BrdU analysis indicated that Sema3A regulated proliferation of ASCs. These findings suggest that Sema3A signaling can modulate expression of Pax7, Myf5, and MyoD. Moreover, we found that expression of emerin, an inner nuclear membrane protein, was regulated by Sema3A signaling. Emerin was identified by positional cloning as the gene responsible for the X-linked form of Emery-Dreifuss muscular dystrophy (X-EDMD). In conclusion, our results support a role for Sema3A in maintaining ASCs through regulation, via emerin, of Pax7, Myf5, and MyoD expression.
authors.affiliation: Department of Animal and Marine Bioresource Sciences Graduate School of Agriculture Kyushu University Hakozaki Fukuoka Japan.
authors.forename: Mulan
authors.initials: M
authors.lastname: Qahar
authors.affiliation: Department of Animal and Marine Bioresource Sciences Graduate School of Agriculture Kyushu University Hakozaki Fukuoka Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takuma
authors.affiliation: Department of Animal and Marine Bioresource Sciences Graduate School of Agriculture Kyushu University Hakozaki Fukuoka Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Mizunoya
authors.affiliation: Department of Animal and Marine Bioresource Sciences Graduate School of Agriculture Kyushu University Hakozaki Fukuoka Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Tatsumi
authors.affiliation: Department of Animal and Marine Bioresource Sciences Graduate School of Agriculture Kyushu University Hakozaki Fukuoka Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Ikeuchi
authors.affiliation: Department of Animal and Marine Bioresource Sciences Graduate School of Agriculture Kyushu University Hakozaki Fukuoka Japan.
authors.forename: Mako
authors.initials: M
authors.lastname: Nakamura
keywords: Myf5; MyoD; Pax7; Sema3A; activated satellite cells; emerin