title: Defective cranial skeletal development, larval lethality and haploinsufficiency in Myod mutant zebrafish.
abstract: Myogenic regulatory factors of the myod family (MRFs) are transcription factors essential for mammalian skeletal myogenesis. Here we show that a mutation in the zebrafish myod gene delays and reduces early somitic and pectoral fin myogenesis, reduces miR-206 expression, and leads to a persistent reduction in somite size until at least the independent feeding stage. A mutation in myog, encoding a second MRF, has little obvious phenotype at early stages, but exacerbates the loss of somitic muscle caused by lack of Myod. Mutation of both myod and myf5 ablates all skeletal muscle. Haploinsufficiency of myod leads to reduced embryonic somite muscle bulk. Lack of Myod causes a severe reduction in cranial musculature, ablating most muscles including the protractor pectoralis, a putative cucullaris homologue. This phenotype is accompanied by a severe dysmorphology of the cartilaginous skeleton and failure of maturation of several cranial bones, including the opercle. As myod expression is restricted to myogenic cells, the data show that myogenesis is essential for proper skeletogenesis in the head.
authors.affiliation: Randall Division for Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, King's College London, SE1 1UL, UK.
authors.forename: Yaniv
authors.initials: Y
authors.lastname: Hinits
authors.forename: Victoria C
authors.initials: VC
authors.lastname: Williams
authors.forename: Dylan
authors.initials: D
authors.lastname: Sweetman
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Donn
authors.forename: Taylur P
authors.initials: TP
authors.lastname: Ma
authors.forename: Cecilia B
authors.initials: CB
authors.lastname: Moens
authors.forename: Simon M
authors.initials: SM
authors.lastname: Hughes
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000196:embryology*; D002356:Cartilage / Q000196:embryology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D057895:Haploinsufficiency / Q000235:genetics* / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007814:Larva / Q000502:physiology; D024510:Muscle Development / Q000502:physiology*; D018482:Muscle, Skeletal / Q000196:embryology; D009154:Mutation / Q000235:genetics; D017570:MyoD Protein / Q000235:genetics* / Q000378:metabolism; D012886:Skull / Q000196:embryology*; D034941:Upper Extremity / Q000196:embryology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics
chemical_list: D017570:MyoD Protein