The concerted action of Meox homeobox genes is required upstream of genetic pathways essential for the formation, patterning and differentiation of somites.
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.
Mankoo
Baljinder S
BS
Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Skuntz
Susan
S
Harrigan
Ian
I
Grigorieva
Elena
E
Candia
Al
A
Wright
Christopher V E
CV
Arnheiter
Heinz
H
Pachnis
Vassilis
V
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*