title: The concerted action of Meox homeobox genes is required upstream of genetic pathways essential for the formation, patterning and differentiation of somites.
abstract: The paraxial mesoderm of the somites of the vertebrate embryo contains the precursors of the axial skeleton, skeletal muscles and dermis. The Meox1 and Meox2 homeobox genes are expressed in the somites and their derivatives during embryogenesis. Mice homozygous for a null mutation in Meox1 display relatively mild defects in sclerotome derived vertebral and rib bones, whereas absence of Meox2 function leads to defective differentiation and morphogenesis of the limb muscles. By contrast, mice carrying null mutations for both Meox genes display a dramatic and wide-ranging synthetic phenotype associated with extremely disrupted somite morphogenesis, patterning and differentiation. Mutant animals lack an axial skeleton and skeletal muscles are severely deficient. Our results demonstrate that Meox1 and Meox2 genes function together and upstream of several genetic hierarchies that are required for the development of somites. In particular, our studies place Meox gene function upstream of Pax genes in the regulation of chondrogenic and myogenic differentiation of paraxial mesoderm.
authors.affiliation: Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Baljinder S
authors.initials: BS
authors.lastname: Mankoo
authors.forename: Susan
authors.initials: S
authors.lastname: Skuntz
authors.forename: Ian
authors.initials: I
authors.lastname: Harrigan
authors.forename: Elena
authors.initials: E
authors.lastname: Grigorieva
authors.forename: Al
authors.initials: A
authors.lastname: Candia
authors.forename: Christopher V E
authors.initials: CV
authors.lastname: Wright
authors.forename: Heinz
authors.initials: H
authors.lastname: Arnheiter
authors.forename: Vassilis
authors.initials: V
authors.lastname: Pachnis
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D001846:Bone Development / Q000502:physiology; D001842:Bone and Bones / Q000002:abnormalities; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology*; D004848:Epithelium / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000502:physiology; D018482:Muscle, Skeletal / Q000002:abnormalities / Q000196:embryology; D010641:Phenotype; D019170:Somites / Q000502:physiology*