MECHANISMS OF LIMB INITIATION AND APICAL ECTODERMAL RIDGE FORMATION

肢体起始和顶端外胚层脊形成的机制

• 批准号: 6311632
• 负责人: CAROLINE N DEALY
• 金额: $ 13.33万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6311632
• 关键词: binding proteins; biological signal transduction; chick embryo; developmental genetics; ectoderm; fibroblast growth factor; gene expression; genetically modified animals; growth factor receptors; histogenesis; homeobox genes; in situ hybridization; insulin; insulinlike growth factor; laboratory mouse; limbs; mesoderm; mutant; polymerase chain reaction; protein isoforms; transforming growth factors; vertebrate embryology

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.

项目2的主要目标（卡罗琳N。Dealy）将研究 参与肢体启动的机制。先前的研究表明， IGF-1是内侧到外侧信号级联的关键组分， 结果建立了推定的肢体领土， 侧板和在最初形成的肢芽从这些 地区 FGF-10最近也参与了这些过程。 关于IGF-1在肢体发育中作用的研究将得到扩展： 将探讨IGF结合蛋白在此过程中的可能作用; 以及IGF-1和FGF-10之间可能的调节关系 将研究初始肢体形成。TGF-α，如IGF-I和FGF-10 在假定肢的中胚层中特异表达 领土，但在干预非肢体形成侧翼。因此 将研究TGF-α在肢体起始中的可能作用。TGF-α 在推定的AER中也有高度特异性表达， 它可能在确定或 将研究AER的质量标准。含有同源框的 Dlx-5基因是果蝇Distal-less基因的脊椎动物同源物， 这是苍蝇胚胎中肢体形成的第一个遗传信号之一。 Dlx-5在假定肢体中高度特异性表达 形成区域的侧板的鸡胚，但不是在 侧翼此外，Dlx-5表达在侧腹中被快速诱导， 在FGF诱导的异位肢体形成过程中。因此， Dlx-5在肢体启动中的作用将被研究， 调节关系IGF-I，FGF-10，和TGF-α的过程中。 项目的第二个目标将是使用amelic的肢芽 突变无肢和无翅鸡胚，以探索FGFR 2的作用 发信号。Wnt 3a和Cux在调节AER形成中的作用。