Ngo-Muller V, Muneoka K
Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana, 70118, USA.
Dev Biol. 2000 Mar 15;219(2):224-36. doi: 10.1006/dbio.2000.9612.
Much of what we currently know about digit morphogenesis during limb development is deduced from embryonic studies in the chick. In this study, we used ex utero surgical procedures to study digit morphogenesis during mouse embryogenesis. Our studies reveal some similarities; however, we have found considerable differences in how the chick and the mouse autopods respond to experimentation. First, we are not able to induce ectopic digit formation from interdigital cells as a result of wounding or TGFbeta-1 application in the mouse, in contrast to what is observed in the chick. Second, FGF4, which inhibits the formation of ectopic digits in the chick, induces a digit bifurcation response in the mouse. We demonstrate with cell marking studies that this bifurcation response results from a reorganization of the prechondrogenic tip of the digit rudiment. The FGF4 effect on digit morphogenesis correlates with changes in the expression of a number of genes, including Msx1, Igf2, and the posterior members of the HoxD cluster. In addition, the bifurcation response is digit-specific, being restricted to digit IV. We propose that FGF4 is an endogenous signal essential for skeletal branching morphogenesis in the mouse. This work stresses the existence of major differences between the chick and the mouse in how digit morphogenesis is regulated and is thus consistent with the view that vertebrate digit evolution is a relatively recent event. Finally, we discuss the relationship between the digit IV bifurcation restriction and the placement of the metapterygial axis in the evolution of the tetrapod limb.
我们目前对肢体发育过程中趾形态发生的许多了解都是从鸡的胚胎研究中推断出来的。在本研究中，我们采用子宫外手术程序来研究小鼠胚胎发育过程中的趾形态发生。我们的研究揭示了一些相似之处；然而，我们发现鸡和小鼠的 autopods 对实验的反应存在相当大的差异。首先，与在鸡中观察到的情况相反，在小鼠中，由于受伤或应用 TGFbeta-1，我们无法从指间细胞诱导异位趾形成。其次，在鸡中抑制异位趾形成的 FGF4 在小鼠中诱导趾分叉反应。我们通过细胞标记研究证明，这种分叉反应是由趾原基软骨前体尖端的重组引起的。FGF4 对趾形态发生的影响与包括 Msx1、Igf2 和 HoxD 簇后部成员在内的一些基因表达的变化相关。此外，分叉反应是趾特异性的，仅限于趾 IV。我们提出 FGF4 是小鼠骨骼分支形态发生所必需的内源性信号。这项工作强调了鸡和小鼠在趾形态发生调控方式上存在重大差异，因此与脊椎动物趾进化是相对较新事件的观点一致。最后，我们讨论了趾 IV 分叉限制与四足动物肢体进化中鳍轴位置之间的关系。
