title: Role of skeletal muscle in ear development.
abstract: The current paper is a continuation of our work described in Rot and Kablar, 2010. Here, we show lists of 10 up- and 87 down-regulated genes obtained by a cDNA microarray analysis that compared developing Myf5-/-:Myod-/- (and Mrf4-/-) petrous part of the temporal bone, containing middle and inner ear, to the control, at embryonic day 18.5. Myf5-/-:Myod-/- fetuses entirely lack skeletal myoblasts and muscles. They are unable to move their head, which interferes with the perception of angular acceleration. Previously, we showed that the inner ear areas most affected in Myf5-/-:Myod-/- fetuses were the vestibular cristae ampullaris, sensitive to angular acceleration. Our finding that the type I hair cells were absent in the mutants' cristae was further used here to identify a profile of genes specific to the lacking cell type. Microarrays followed by a detailed consultation of web-accessible mouse databases allowed us to identify 6 candidate genes with a possible role in the development of the inner ear sensory organs: Actc1, Pgam2, Ldb3, Eno3, Hspb7 and Smpx. Additionally, we searched for human homologues of the candidate genes since a number of syndromes in humans have associated inner ear abnormalities. Mutations in one of our candidate genes, Smpx, have been reported as the cause of X-linked deafness in humans. Our current study suggests an epigenetic role that mechanical, and potentially other, stimuli originating from muscle, play in organogenesis, and offers an approach to finding novel genes responsible for altered inner ear phenotypes.
authors.affiliation: Department of Medical Neuroscience (Division of Anatomy), Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
authors.forename: Irena
authors.initials: I
authors.lastname: Rot
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Baguma-Nibasheka
authors.affiliation: Human Health Therapeutics, Translational Bioscience, National Research Council, Ottawa, ON, Canada.
authors.forename: Willard J
authors.initials: WJ
authors.lastname: Costain
authors.affiliation: IWK Health Centre, Department of Surgery, Dalhousie University, Halifax, NS, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Hong
authors.affiliation: Department of Otorhinolaryngology, University Hospital in Split, Split, Croatia.
authors.forename: Robert
authors.initials: R
authors.lastname: Tafra
authors.affiliation: Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, Split, Croatia.
authors.forename: Snjezana
authors.initials: S
authors.lastname: Mardesic-Brakus
authors.affiliation: Department of Family Medicine, School of Medicine, University of Split, Split, Croatia.
authors.forename: Natasa
authors.initials: N
authors.lastname: Mrduljas-Djujic
authors.affiliation: Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, Split, Croatia.
authors.forename: Mirna
authors.initials: M
authors.lastname: Saraga-Babic
authors.affiliation: Department of Medical Neuroscience (Division of Anatomy), Faculty of Medicine, Dalhousie University, Halifax, NS, Canada. bkablar@dal.ca.
authors.forename: Boris
authors.initials: B
authors.lastname: Kablar
mesh_terms: D000818:Animals; D004423:Ear / Q000196:embryology / Q000254:growth & development*; D007758:Ear, Inner / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006199:Hair Cells, Auditory, Inner / Q000502:physiology; D006801:Humans; D051379:Mice; D046228:Microarray Analysis; D018482:Muscle, Skeletal / Q000502:physiology*; D038081:Organogenesis