Rodriguez-Esteban C, Tsukui T, Yonei S, Magallon J, Tamura K, Izpisua Belmonte J C
Gene Expression Laboratory, The Salk Institute, La Jolla, California 92037-1099, USA.
Nature. 1999 Apr 29;398(6730):814-8. doi: 10.1038/19769.
During embryonic development, initially similar fields can develop into distinct structures, such as the vertebrate fore- and hindlimbs. Although considerable progress has been made in our understanding of the genetic control underlying the establishment of the different limb axes, the molecular cues that specify the differential development of the fore- and hindlimbs are unknown. Possible candidates for genes determining limb identity are Pitx1, a gene whose transcripts are detected in the early hind- but not forelimb bud, and two members of the T-box (Tbx) gene family, Tbx4 and Tbx5, which are specifically expressed in the hindlimb and forelimb buds, respectively. Here we show that Tbx4 and Tbx5 are essential regulators of limb outgrowth whose roles seem to be tightly linked to the activity of three signalling proteins that are required for limb outgrowth and patterning: fibroblast growth factor (FGF), bone morphogenetic protein (BMP) and Wnt. In addition, we provide evidence that Tbx4 and Tbx5 are involved in controlling limb identity. Our findings provide insight into how similar developmental fields can evolve into homologous but distinct structures.
在胚胎发育过程中，最初相似的区域能够发育成不同的结构，比如脊椎动物的前肢和后肢。尽管我们在理解不同肢体轴建立背后的遗传控制方面已经取得了相当大的进展，但决定前肢和后肢差异发育的分子线索仍然未知。确定肢体特征的可能候选基因是Pitx1，该基因的转录本在早期后肢芽而非前肢芽中被检测到，以及T-box（Tbx）基因家族的两个成员Tbx4和Tbx5，它们分别在前肢芽和后肢芽中特异性表达。在这里，我们表明Tbx4和Tbx5是肢体生长的关键调节因子，它们的作用似乎与肢体生长和模式形成所需的三种信号蛋白的活性紧密相关：成纤维细胞生长因子（FGF）、骨形态发生蛋白（BMP）和Wnt。此外，我们提供证据表明Tbx4和Tbx5参与控制肢体特征。我们的研究结果为相似的发育区域如何演变成同源但不同的结构提供了见解。
