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-II在肿瘤生长中的作用。 胰岛素在肢芽的初始形成中起重要作用 鸡胚;在AER的诱导中;以及，在随后的 AER和亚脊中胚层之间的相互作用， 负责肢体的继续生长。 初步研究 表明IGF-I能够诱导肢芽的形成， 鸡外侧板的预期肢体形成区 胚胎在发展阶段时，这个地区还没有获得 独立于中间胚胎组织形成肢体的能力。 因此 IGF-I和胰岛素在诱导信号级联中的作用 在中间组织（中间中胚层，体节中胚层，和 Hensen结）和外侧板的预期肢体形成区域 这赋予了假定的肢中胚层与肢形成区的 赋予假定肢中胚层肢形成的侧板 能力，将被调查。 还将确定IGF-i和IGF-b是否存在。 胰岛素可以诱导正常不形成肢体的侧翼形成肢体 如果IGF-I和胰岛素可以诱导AER， 体内外侧外胚层。 IGF-I和胰岛素在糖尿病中的作用 AER/亚嵴相互作用需要持续的肢体生长， 还将检查肢体形成。 初步体外研究 表明这些生长因子参与了促进生长 并抑制脊下中胚层响应于 AER，也可能在AER活动中。 IGF-I和胰岛素的作用 将研究AER活性的维持和/或调节， 将确定这些生长因子是否能促进生长， 肢体中胚层的形态发生在体内的AER的情况下。 的 IGF-I、胰岛素和FGF之间的调节关系， 涉及介导AER的生长和图案化效应， 将被研究。

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.