SONIC HEDGEHOG AND FGF-4 ACT THROUGH A SIGNALING CASCADE AND FEEDBACK LOOP TO INTEGRATE GROWTH AND PATTERNING OF THE DEVELOPING LIMB BUD
SONIC HEDGEHOG AND FGF-4 ACT THROUGH A SIGNALING CASCADE AND FEEDBACK LOOP TO INTEGRATE GROWTH AND PATTERNING OF THE DEVELOPING LIMB BUD
复制标题
DOI：
10.1016/0092-8674(94)90030-2
复制
发表时间：
1994-12-16
期刊：
影响因子：
64.5
通讯作者：
TABIN, C
中科院分区：
文献类型：
--
作者：
LAUFER, E;NELSON, CE;TABIN, C
正确的肢体生长和图案需要来自后中胚层极化活动区和上覆的顶端外胚层嵴（AER）的信号。Sonic hedgehog和FGF-4最近分别被确定为这些信号的候选者。我们已经解剖了这些分泌蛋白在早期肢体发育中的作用，通过异位调节它们在一些手术环境中的活性。我们的研究结果表明，Sonic hedgehog启动二级信号分子的表达，包括中胚层中的BMP-2和外胚层中的FGF-4。中胚层需要外胚层衍生的感受态因子，包括FGF-4，以响应Sonic hedgehog激活靶基因表达。Sonic hedgehog和Fgf-4的表达受后中胚层和上覆AER之间的正反馈回路的协调调节。总而言之，这些数据为了解发育肢体中生长和模式的整合提供了基础。
Proper limb growth and patterning requires signals from the zone of polarizing activity in the posterior mesoderm and from the overlying apical ectodermal ridge (AER). Sonic hedgehog and Fgf-4, respectively, have recently been identified as candidates for these signals. We have dissected the roles of these secreted proteins in early limb development by ectopically regulating their activities in a number of surgical contexts. Our results indicate that Sonic hedgehog initiates expression of secondary signaling molecules, including Bmp-2 in the mesoderm and Fgf-4 in the ectoderm. The mesoderm requires ectodermally derived competence factors, which include Fgf-4, to activate target gene expression in response to Sonic hedgehog. The expression of Sonic hedgehog and Fgf-4 is coordinately regulated by a positive feedback loop operating between the posterior mesoderm and the overlying AER. Taken together, these data provide a basis for understanding the integration of growth and patterning in the developing limb.