IGF-1 AND INSULIN IN LIMB FORMATION AND MORPHOGENESIS

项目2的目标是研究生长因子IGF-I和IGF-I的作用 胰岛素在四肢侧板起始形成中的作用 鸡胚；在AER的诱导过程中；以及在随后的 AER和亚脊中胚层之间的相互作用 对肢体的持续生长负责。初步研究 提示IGF-I能够诱导小鼠的肢芽形成。 雏鸡侧板的预期肢体形成区 胚胎处于发育阶段，而这个地区还没有获得 形成独立于胚胎内侧组织的四肢的能力。因此， 胰岛素样生长因子-I和胰岛素在诱导信号级联反应中的作用 中间组织(中间中胚层、体细胞中胚层和 Hensen‘s Node)和侧板的预期肢体形成区 这赋予了假定的肢体中胚层具有 使假定的肢体中胚层具有成肢作用的侧板 容量，将进行调查。还将确定IGF-I和IGF-I是否 胰岛素可以从正常的非肢体形成侧翼诱导肢体形成 侧板区域，以及IGF-I和胰岛素是否能在 侧翼外胚层的体外和体内实验。胰岛素样生长因子-I和胰岛素在血管紧张素转换酶中的作用 持续肢体生长所需的AER/亚脊相互作用 肢体的形成也将被检查。初步的体外研究 表明这些生长因子参与了促进生长的过程。 以及抑制亚脊中胚层的分化以响应 AER，也可能在AER活动中。胰岛素样生长因子-I与胰岛素的作用 将研究AER活性的维持和/或调节，以及 将确定这些生长因素是否能促进生长和 体内无AER条件下肢体中胚层的形态发生。这个 胰岛素样生长因子-I、胰岛素和成纤维细胞生长因子之间的调节关系 与调节AER的生长和图案化效应有关， 将会被研究。

The goal of Project 2 is to study the roles of the growth factors IGF-I and insulin in th initial formation of the limb bud from the lateral plate of the chick embryo; in the induction of the AER; and, in the subsequent reciprocal interactions between the AER and subridge mesoderm that are responsible for continued outgrowth of the limb. Preliminary studies indicate that IGF-I is capable of inducing the formation of limb buds from the prospective limb-forming region of the lateral plate of the chick embryo at a stage of development when this region has not yet acquired the ability to form limbs independent of medial embryonic tissues. Thus, the role of IGF-I as well as insulin, in the inductive signalling cascade between medial tissues (intermediate mesoderm, somitic mesoderm, and Hensen's node) and the prospective limb-forming region of the lateral plate that endows presumptive limb mesoderm with limb-forming region of the lateral plate that endows presumptive limb mesoderm with limb-forming capacity, will be investigated. It will also be determined if IGF-i and insulin can induce limb formation from the normally non-limb-forming flank region of the lateral plate, and if IGF-I and insulin can induce an AER in flank ectoderm in vitro and in vivo. The role of IGF-I and insulin in the AER/subridge interactions required for continued limb outgrowth following limb formation will also be examined. Preliminary in vitro studies indicate that these growth factors are involved in promoting the outgrowth and suppressing the differentiation of the subridge mesoderm in response to the AER, and also possibly in AER activity. The role of IGF-I and insulin in the maintenance and/or regulation of AER activity will be studied, and it will be determined if these growth factors can promote the outgrowth and morphogenesis of limb mesoderm in the absence of the AER in vivo. The regulatory relationships between IGF-I, insulin, and FGFs, which have been implicated in mediating the outgrowth and patterning effects of the AER, will be studied.