Misexpression of Hoxa-13 induces cartilage homeotic transformation and changes cell adhesiveness in chick limb buds.
Misexpression of Hoxa-13 induces cartilage homeotic transformation and changes cell adhesiveness in chick limb buds.
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DOI：
10.1101/gad.9.20.2509
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发表时间：
1995-10
影响因子：
10.5
通讯作者：
Y. Yokouchi;S. Nakazato;Masakazu Yamamoto;Y. Goto;Takashi Kameda;Hideo Iba;Atsushi Kuroiwa
中科院分区：
文献类型：
--
作者：
Y. Yokouchi;S. Nakazato;Masakazu Yamamoto;Y. Goto;Takashi Kameda;Hideo Iba;Atsushi Kuroiwa
在鸡肢体发育过程中，Abd-B亚家族基因在HoxA簇中以区域特异性方式沿proximodistal轴沿着表达。为了阐明Hoxa-13在正常肢体发育过程中在足中表达的功能，Hoxa-13在具有复制能力的逆转录病毒系统的整个肢体芽中错误表达。Hoxa-13的错误表达导致关节软骨的尺寸显著减小，这是由于关节软骨细胞的生长和分化受到限制。这种大小的减少似乎是由于同源异型转化的软骨在zeugopod更远的软骨，即腕骨/跗骨。这种转化是特异性的Hoxa-13，并没有观察到其他Hox基因的过表达。这些结果表明，在正常发育过程中，Hoxa-13负责将遗传密码从长骨形成转换为短骨形成。当肢体间充质细胞分离并在体外培养时，表达Hoxa-13的肢体间充质细胞重新结合并从非表达细胞中分选出来。在内源性Hoxa-13尚未表达的阶段强制表达Hoxa-13改变了嗜同性细胞粘附性质。这些发现表明Hoxa-13参与决定同种细胞间的相互作用，这对软骨模式的形成至关重要。
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.