Paulsen D F
Department of Anatomy, Morehouse School of Medicine, Atlanta, GA 30310.
Anat Embryol (Berl). 1994 Nov;190(5):399-415. doi: 10.1007/BF00235487.
Limb outgrowth is arguably the most fundamental aspect of limb development. It begins with the emergence of buds from the embryo's lateral body wall. More rapid growth along each bud's proximodistal axis than along its anteroposterior or dorsoventral axes yields the limb's basic elongated shape. Many processes that generate refinements of this basic limb form are now being explored at the molecular level. Yet, there remain gaps in our understanding of basic limb outgrowth itself. This review examines the pivotal role of the apical ectodermal ridge in promoting and maintaining limb-bud outgrowth. It discusses the interplay between the apical ectodermal ridge and the subridge limb mesenchyme. It examines evidence that the pattern of limb anomalies in the offspring of mothers exposed to exogenous retinoids such as retinoic acid strongly suggests interference with apical ectodermal ridge function. It covers evidence that cellular retinoic acid-binding protein in the cytoplasm of the cells under the apical ectodermal ridge limits the effects of retinoic acid, a potent retinoid and teratogen, on retinoic acid-driven gene transcription. It explains that retinoic acid generally enhances differentiation in a variety of cell types. On the basis of the information presented, it is suggested that the limb ectoderm promotes cellular retinoic acid-binding protein expression in the subridge mesenchyme and thereby limits the access of retinoic acid to its nuclear receptors in these cells. Cellular-retinoic-acid-binding-protein-mediated, local sequestration or inactivation of free retinoic acid is suggested as a prerequisite not only for the continued responsiveness of the distal mesenchyme to growth promotion by the apical ectodermal ridge, but to the maintenance of the apical ectodermal ridge itself by the subridge mesenchyme.
肢体生长可以说是肢体发育最基本的方面。它始于胚胎侧体壁上芽的出现。沿着每个芽的近远轴比沿着其前后轴或背腹轴生长得更快，从而产生了肢体的基本细长形状。目前正在分子水平上探索许多使这种基本肢体形态更加精细的过程。然而，我们对基本肢体生长本身的理解仍存在空白。这篇综述探讨了顶端外胚层嵴在促进和维持肢体芽生长中的关键作用。它讨论了顶端外胚层嵴与嵴下肢体间充质之间的相互作用。它研究了证据，即接触外源性类视黄醇如视黄酸的母亲所生后代的肢体异常模式强烈表明对顶端外胚层嵴功能的干扰。它涵盖了证据，即顶端外胚层嵴下方细胞胞质中的细胞视黄酸结合蛋白限制了视黄酸（一种有效的类视黄醇和致畸剂）对视黄酸驱动的基因转录的影响。它解释说视黄酸通常会增强多种细胞类型的分化。根据所提供的信息，有人提出肢体外胚层促进嵴下间充质中细胞视黄酸结合蛋白的表达，从而限制视黄酸进入这些细胞中的核受体。细胞视黄酸结合蛋白介导的游离视黄酸的局部隔离或失活不仅被认为是远端间充质对顶端外胚层嵴促进生长持续反应的先决条件，也是嵴下间充质维持顶端外胚层嵴本身的先决条件。
