title: ATOH8, a regulator of skeletal myogenesis in the hypaxial myotome of the trunk.
abstract: The embryonic muscles of the axial skeleton and limbs take their origin from the dermomyotomes of the somites. During embryonic myogenesis, muscle precursors delaminate from the dermomyotome giving rise to the hypaxial and epaxial myotome. Mutant studies for myogenic regulatory factors have shown that the development of the hypaxial myotome differs from the formation of the epaxial myotome and that the development of the hypaxial myotome depends on the latter within the trunk region. The transcriptional networks that regulate the transition of proliferative dermomyotomal cells into the predominantly post-mitotic hypaxial myotome, as well as the eventual patterning of the myotome, are not fully understood. Similar transitions occurring during the development of the neural system have been shown to be controlled by the Atonal family of helix-loop-helix transcription factors. Here, we demonstrate that ATOH8, a member of the Atonal family, is expressed in a subset of embryonic muscle cells in the dermomyotome and myotome. Using the RNAi approach, we show that loss of ATOH8 in the lateral somites at the trunk level results in a blockage of differentiation and thus causes cells to be maintained in a predetermined state. Furthermore, we show that ATOH8 is also expressed in cultured C2C12 mouse myoblasts and becomes dramatically downregulated during their differentiation. We propose that ATOH8 plays a role during the transition of myoblasts from the proliferative phase to the differentiation phase and in the regulation of myogenesis in the hypaxial myotome of the trunk.
authors.affiliation: Department of Anatomy and Molecular Embryology, Institute of Anatomy, Ruhr University Bochum, 44801, Bochum, Germany, ajeesh.br@gmail.com.
authors.forename: Ajeesh
authors.initials: A
authors.lastname: Balakrishnan-Renuka
authors.forename: Gabriela
authors.initials: G
authors.lastname: Morosan-Puopolo
authors.forename: Faisal
authors.initials: F
authors.lastname: Yusuf
authors.forename: Aisha
authors.initials: A
authors.lastname: Abduelmula
authors.forename: Jingchen
authors.initials: J
authors.lastname: Chen
authors.forename: Georg
authors.initials: G
authors.lastname: Zoidl
authors.forename: Susanne
authors.initials: S
authors.lastname: Philippi
authors.forename: Fangping
authors.initials: F
authors.lastname: Dai
authors.forename: Beate
authors.initials: B
authors.lastname: Brand-Saberi
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics*; D019521:Body Patterning / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D019070:Cell Lineage; D002642:Chick Embryo; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D024510:Muscle Development / Q000235:genetics*; D018482:Muscle, Skeletal / Q000196:embryology*; D032446:Myoblasts / Q000166:cytology; D051787:Myogenic Regulatory Factor 5 / Q000096:biosynthesis; D018008:Myogenin / Q000096:biosynthesis; D051763:PAX7 Transcription Factor / Q000096:biosynthesis; D034622:RNA Interference; D034741:RNA, Small Interfering; D019170:Somites / Q000502:physiology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin; D051763:PAX7 Transcription Factor; D034741:RNA, Small Interfering; C449163:Atoh8 protein, mouse