MECHANISMS OF LIMB INITIATION AND APICAL ECTODERMAL RIDGE FORMATION

项目2(Caroline N.Dealy)的主要目标将是研究 参与肢体启动的机制。此前的研究表明， IGF-1是内侧到外侧信号级联的关键组成部分， 结果确定了推定的 侧板和在肢芽的初始形成中 地区。最近，成纤维细胞生长因子-10也参与了这些过程。 关于IGF-1在肢体启动中的作用的研究将会扩大： 将探索IGF结合蛋白在这一过程中的可能作用； 胰岛素样生长因子-I和成纤维细胞生长因子-10之间可能的调控关系 将研究最初的肢体形成。转化生长因子-α，如胰岛素样生长因子-I和成纤维细胞生长因子-10 在假定肢体的中胚层中特异表达 领土，但在中间的非肢体形成侧翼。因此， 将研究转化生长因子-α在肢体起始中的可能作用。转化生长因子-α 在假定的AER中也得到了高度和明确的表达，因此 它可能发挥决定作用的可能性或 将对AER的规格进行调查。含有同源异型盒的 DLX-5基因是果蝇Distal-less的脊椎动物同源物，它是 在果蝇胚胎中形成肢体的最早的遗传信号之一。 DLX-5在假肢中高度特异表达 雏鸡胚胎侧板的形成区域，但不在 侧翼。此外，DLX-5在侧翼被迅速诱导表达 在成纤维细胞生长因子诱导的异位肢体形成过程中。因此，这一角色 将研究DLX-5在肢体启动中的作用，以及它的可能性 在这一过程中对IGF-I、成纤维细胞生长因子-10和转化生长因子-α的调控关系。 项目的次要目标将是利用釉质的肢芽 突变鸡胚胎无肢和无翼探讨FGFR2的作用 发信号。Wnt3a和Cux在调节AER的形成中的作用。

The primary goal of Project 2 (Caroline N. Dealy) will be to study the mechanisms involved in limb initiation. Previous studies indicate that IGF-1 is a key component of a medial to lateral signaling cascade that results in the establishment of the presumptive limb territories of the lateral plate and in the initial formation of the limb bud from these regions. FGF-10 has also recently been implicated in these processes. Studies on the role of IGF-1 in limb initiation will be expanded: the possible role of IGF binding proteins in the process will be explored; and the possible regulatory relationship between IGF-I and FGF-10 initial limb formation will be studied. TGF-alpha, like IGF-I and FGF-10 is specifically expressed in the mesoderm of the presumptive limb territories, but in the intervening non-limb forming flank. Thus, the possible role of TGF-alpha in limb initiation will be studied. TGF-alpha is also highly and specifically expressed in the presumptive AER, and so the possibility that it may play a role in determination or specification of the AER will be investigated. The homeobox-containing gene Dlx-5 is vertebrate homolog of the Drosophila Distal-less, which is one of the first genetic signals for limb formation in the fly embryo. Dlx-5 is highly and specifically expressed in the presumptive limb forming regions of the lateral plate of the chick embryo, but not in the flank. Furthermore, Dlx-5 expression is rapidly induced in the flank during the formation of FGF-induced ectopic limbs. Thus, the role of Dlx-5 in limb initiation will be studied, as will its possible regulatory relationships to IGF-I, FGF-10, and TGF-alpha in the process. A secondary goal of Projects will be to use the limb buds of the amelic mutant chick embryos limbless and wingless to explore the roles of FGFR2 signaling. Wnt3a, and Cux in regulating formation of the AER.