Mankoo Baljinder S, Skuntz Susan, Harrigan Ian, Grigorieva Elena, Candia Al, Wright Christopher V E, Arnheiter Heinz, Pachnis Vassilis
Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Development. 2003 Oct;130(19):4655-64. doi: 10.1242/dev.00687.
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.
脊椎动物胚胎体节的近轴中胚层包含轴向骨骼、骨骼肌和真皮的前体。Meox1和Meox2同源框基因在胚胎发生过程中在体节及其衍生物中表达。Meox1基因纯合无效突变的小鼠在源自生骨节的椎骨和肋骨中表现出相对较轻的缺陷，而缺乏Meox2功能则导致肢体肌肉的分化和形态发生缺陷。相比之下，携带两个Meox基因无效突变的小鼠表现出一种显著且广泛的合成表型，与体节形态发生、模式形成和分化的极度紊乱相关。突变动物缺乏轴向骨骼，骨骼肌严重缺失。我们的结果表明，Meox1和Meox2基因共同发挥作用，且在体节发育所需的几个基因层级的上游发挥作用。特别是，我们的研究表明，在调节近轴中胚层的软骨生成和肌生成分化方面，Meox基因的功能在Pax基因的上游。
