Fernandez-Teran M, Piedra M E, Kathiriya I S, Srivastava D, Rodriguez-Rey J C, Ros M A
Departamento de Anatomía y Biología Celular, Universidad de Cantabria, Spain.
Development. 2000 May;127(10):2133-42. doi: 10.1242/dev.127.10.2133.
dHAND is a basic helix-loop-helix (bHLH) transcription factor essential for cardiovascular development. Here we analyze its pattern of expression and functional role during chick limb development. dHAND expression was observed in the lateral plate mesoderm prior to emergence of the limb buds. Coincident with limb initiation, expression of dHAND became restricted to the posterior half of the limb bud. Experimental procedures that caused mirror-image duplications of the limb resulted in mirror-image duplications of the pattern of dHAND expression along the anterior-posterior axis. Retroviral overexpression of dHAND in the limb bud produced preaxial polydactyly, corresponding to mild polarizing activity at the anterior border. At the molecular level, misexpression of dHAND caused ectopic activation of members of the Sonic hedgehog (Shh) pathway, including Gli and Patched, in the anterior limb bud. A subset of infected embryos displayed ectopic anterior activation of Shh. Other factors implicated in anterior-posterior polarization of the bud such as the most 5' Hoxd genes and Bmp2 were also ectopically activated at the anterior border. Our results indicate a role for dHAND in the establishment of anterior-posterior polarization of the limb bud.
dHAND是一种对心血管发育至关重要的碱性螺旋-环-螺旋（bHLH）转录因子。在此，我们分析其在鸡胚肢体发育过程中的表达模式和功能作用。在肢芽出现之前，dHAND在侧板中胚层中表达。与肢体起始同时，dHAND的表达局限于肢芽的后半部分。导致肢体镜像重复的实验操作致使dHAND表达模式沿前后轴出现镜像重复。在肢芽中逆转录病毒介导的dHAND过表达产生了轴前多指畸形，这与在前缘的轻度极化活性相对应。在分子水平上，dHAND的错误表达导致了前肢芽中Sonic刺猬因子（Shh）信号通路成员（包括Gli和Patched）的异位激活。一部分受感染胚胎在前缘出现了Shh的异位激活。其他与芽的前后极化有关的因子，如最5'端的Hoxd基因和Bmp2，在前缘也被异位激活。我们的结果表明dHAND在肢芽前后极化的建立中发挥作用。
