Gardiner D M, Blumberg B, Komine Y, Bryant S V
Development Biology Center, University of California Irvine 92717, USA.
Development. 1995 Jun;121(6):1731-41. doi: 10.1242/dev.121.6.1731.
Homeobox genes are important in the regulation of outgrowth and pattern formation during limb development. It is likely that homeobox genes play an equally important role during limb regeneration. We have isolated and identified 17 different homeobox-containing genes expressed by cells of regenerating axolotl limbs. Of these, nearly half of the clones represent genes belonging to the HoxA complex, which are thought to be involved in pattern formation along the proximal-distal limb axis. In this paper we report on the expression patterns of two 5' members of this complex, HoxA13 and HoxA9. These genes are expressed in cells of developing limb buds and regenerating blastemas. The pattern of expression in developing axolotl limb buds is comparable to that in mouse and chick limb buds; the expression domain of HoxA13 is more distally restricted than that of HoxA9. As in developing mouse and chick limbs, HoxA13 likely functions in the specification of distal limb structures, and HoxA9 in the specification of more proximal structures. In contrast, during regeneration, HoxA13 and HoxA9 do not follow the rule of spatial colinearity observed in developing limbs. Instead, both genes are initially expressed in the same population of stump cells, giving them a distal Hox code regardless of the level of amputation. In addition, both are reexpressed within 24 hours after amputation, suggesting that reexpression may be synchronous rather than temporally colinear. Treatment with retinoic acid alters this Hox code to that of a more proximal region by the rapid and differential downregulation of HoxA13, at the same time that expression of HoxA9 is unaffected. HoxA reexpression occurs prior to blastema formation, 24-48 hours after amputation, and is an early molecular marker for dedifferentiation.
同源异型盒基因在肢体发育过程中的生长和模式形成调控中起着重要作用。同源异型盒基因在肢体再生过程中可能也发挥着同样重要的作用。我们已经分离并鉴定出17种不同的、由蝾螈再生肢体细胞表达的含同源异型盒基因。其中，近一半的克隆代表属于HoxA复合体的基因，这些基因被认为参与了沿肢体近端 - 远端轴的模式形成。在本文中，我们报告了该复合体的两个5'成员HoxA13和HoxA9的表达模式。这些基因在发育中的肢芽细胞和再生芽基中表达。蝾螈发育中的肢芽中的表达模式与小鼠和鸡的肢芽中的模式相当；HoxA13的表达域比HoxA9的更受远端限制。与发育中的小鼠和鸡的肢体一样，HoxA13可能在远端肢体结构的特化中起作用，而HoxA9在更近端结构的特化中起作用。相比之下，在再生过程中，HoxA13和HoxA9并不遵循在发育肢体中观察到的空间共线性规则。相反，这两个基因最初都在同一群残端细胞中表达，无论截肢水平如何，都赋予它们一个远端Hox编码。此外，两者在截肢后24小时内都会重新表达，这表明重新表达可能是同步的，而不是时间上的共线性。用视黄酸处理通过快速且差异性地下调HoxA13，将这种Hox编码改变为更近端区域的编码，同时HoxA9的表达不受影响。HoxA的重新表达发生在芽基形成之前，截肢后24 - 48小时，并且是去分化的早期分子标记。
