Hayamizu T F, Bryant S V
Developmental Biology Center, University of California, Irvine 92717.
Dev Biol. 1994 Nov;166(1):123-32. doi: 10.1006/dbio.1994.1301.
The finding that retinoic acid (RA) has major effects on pattern formation in developing chick limbs has led to the conclusion that RA plays a central role in the normal development of the limb. In addition, it has been demonstrated that treatment with exogenous RA leads to changes in expression of homeobox-containing Hox complex genes within the developing limb. This has been used to argue that, since RA activates 5' Hox D complex genes in the same temporal and spatial sequence as in normal development, Hox genes might be regulated by RA during normal limb development. In this study, we further examine the temporal and spatial changes in expression of Hox D13 and RAR-beta 2 transcripts in wing buds in response to local application of RA in vivo. We confirm reports that RAR-beta 2 expression is induced early and locally by RA. However, we find that the effect of RA on Hox D13 gene expression at the distal end of wing buds at stage 25/26 is downregulation of transcript expression. Furthermore, we find that activation of ectopic Hox D13 expression in response to implantation of RA beads along the anterior margin at stage 20/21 is indirect. Finally, the effects of RA exposure on Hox D13 expression appear to directly correlate with effects on the pattern of distal skeletal elements.
视黄酸（RA）对发育中的鸡肢体模式形成有重大影响这一发现，已得出RA在肢体正常发育中起核心作用的结论。此外，已证明用外源性RA处理会导致发育中的肢体中含同源框的Hox复合基因表达发生变化。这一点被用来论证，由于RA以与正常发育相同的时间和空间顺序激活5'Hox D复合基因，Hox基因在正常肢体发育过程中可能受RA调控。在本研究中，我们进一步研究了体内局部应用RA后，翼芽中Hox D13和RAR-β2转录本表达的时空变化。我们证实了关于RA早期局部诱导RAR-β2表达的报道。然而，我们发现，在第25/26阶段，RA对翼芽远端Hox D13基因表达的影响是转录本表达下调。此外，我们发现，在第20/21阶段，沿前缘植入RA珠粒后，异位Hox D13表达的激活是间接的。最后，RA暴露对Hox D13表达的影响似乎与对远端骨骼元件模式的影响直接相关。
