Yokouchi Y, Nakazato S, Yamamoto M, Goto Y, Kameda T, Iba H, Kuroiwa A
Department of Molecular Biology, School of Science, Nagoya University, Japan.
Genes Dev. 1995 Oct 15;9(20):2509-22. doi: 10.1101/gad.9.20.2509.
During chick limb development, the Abd-B subfamily of genes in the HoxA cluster are expressed in a region-specific manner along the proximodistal axis. To elucidate the function of Hoxa-13 that is expressed in the autopod during normal limb development, Hoxa-13 was misexpressed in the entire limb bud with a replication-competent retroviral system. Misexpression of Hoxa-13 resulted in a remarkable size reduction of the zeugopodal cartilages as a result of the arrest of cartilage cell growth and differentiation restricted in the zeugopod. This size reduction seems to be attributable to homeotic transformation of the cartilages in the zeugopod to the more distal cartilage, that of the carpus/tarsus. This transformation was specific to Hoxa-13 and was not observed by overexpression of other Hox genes. These results indicate that Hoxa-13 is responsible for switching the genetic code from long bone formation to short bone formation during normal development. When the limb mesenchymal cells were dissociated and cultured in vitro, Hoxa-13-expressing limb mesenchymal cells reassociated and were sorted out from nonexpressing cells. Forced expression of Hoxa-13 at the stage that endogenous Hoxa-13 was not expressed as of yet altered the homophilic cell adhesive property. These findings indicate the involvement of Hoxa-13 in determining homophilic cell-to-cell adhesiveness that is supposed to be crucial for the cartilage pattern formation.
在鸡胚肢体发育过程中，HoxA基因簇中的Abd - B基因亚家族沿近远轴以区域特异性方式表达。为了阐明在正常肢体发育过程中在肢体末端表达的Hoxa - 13的功能，利用具有复制能力的逆转录病毒系统在整个肢体芽中错误表达Hoxa - 13。Hoxa - 13的错误表达导致中间腕骨软骨显著变小，这是由于软骨细胞生长和分化停滞局限于中间腕骨。这种尺寸减小似乎归因于中间腕骨的软骨向更远端的软骨（腕骨/跗骨的软骨）的同源异型转化。这种转化是Hoxa - 13特有的，其他Hox基因的过表达未观察到这种现象。这些结果表明，Hoxa - 13在正常发育过程中负责将遗传编码从长骨形成切换为短骨形成。当肢体间充质细胞解离并在体外培养时，表达Hoxa - 13的肢体间充质细胞重新聚集并与未表达的细胞分离。在内源性Hoxa - 13尚未表达的阶段强制表达Hoxa - 13改变了嗜同性细胞黏附特性。这些发现表明Hoxa - 13参与决定嗜同性细胞间黏附性，而这对软骨模式形成至关重要。
