title: Six family genes control the proliferation and differentiation of muscle satellite cells.
abstract: Muscle satellite cells are essential for muscle growth and regeneration and their morphology, behavior and gene expression have been extensively studied. However, the mechanisms involved in their proliferation and differentiation remain elusive. Six1 and Six4 proteins were expressed in the nuclei of myofibers of adult mice and the numbers of myoblasts positive for Six1 and Six4 increased during regeneration of skeletal muscles. Six1 and Six4 were expressed in quiescent, activated and differentiated muscle satellite cells isolated from adult skeletal muscle. Overexpression of Six4 and Six5 repressed the proliferation and differentiation of satellite cells. Conversely, knockdown of Six5 resulted in augmented proliferation, and that of Six4 inhibited differentiation. Muscle satellite cells isolated from Six4(+/-)Six5(-/-) mice proliferated to higher cell density though their differentiation was not altered. Meanwhile, overproduction of Six1 repressed proliferation and promoted differentiation of satellite cells. In addition, Six4 and Six5 repressed, while Six1 activated myogenin expression, suggesting that the differential regulation of myogenin expression is responsible for the differential effects of Six genes. The results indicated the involvement of Six genes in the behavior of satellite cells and identified Six genes as potential target for manipulation of proliferation and differentiation of muscle satellite cells for therapeutic applications.
authors.affiliation: Division of Biology, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yajima
authors.forename: Norio
authors.initials: N
authors.lastname: Motohashi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ono
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sato
authors.forename: Keiko
authors.initials: K
authors.lastname: Ikeda
authors.forename: Satoru
authors.initials: S
authors.lastname: Masuda
authors.forename: Erica
authors.initials: E
authors.lastname: Yada
authors.forename: Hironori
authors.initials: H
authors.lastname: Kanesaki
authors.forename: Yuko
authors.initials: Y
authors.lastname: Miyagoe-Suzuki
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Takeda
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kawakami
mesh_terms: D000328:Adult; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D005786:Gene Expression Regulation / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D032342:Muscle Cells / Q000166:cytology; D018008:Myogenin / Q000096:biosynthesis; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology*; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology
chemical_list: D018398:Homeodomain Proteins; D018008:Myogenin; C098490:Six4 protein, mouse; C486344:Six5 protein, mouse; D015534:Trans-Activators