PATTERN FORMATION IN THE VERTIBRATE GUT

描述(改编自调查人员摘要)：本提案概述 使用雏鸡胃肠道作为模型系统 研究内脏发育的分子调控。肠道是由以下因素形成的 胚胎前后两极均有内陷。后续 延长、折叠和细胞分化导致闭合的管子 与大体形态和功能上的区别 前/后(AP)轴。该AP轴被区域化以形成 成人前、中、后肠道内胚层/中胚层的形态 (EM)信号在肠道的启动和形态发生中都是必不可少的 管子发育和形成肠道衍生物(如胰腺和肺)。 这一建议解决了AP肠道模式的分子控制问题。 果蝇肠道发育调控基因的几个同源基因是 在脊椎动物的肠道中以指示潜力的模式表达 功能保守，包括HOX基因。具体目标是 旨在研究这一假说：HOX基因在 建立脊椎动物的大体、显微和分子模式 直觉。利用小鸡系统的功能，病毒介导的错误- 在卵子和器官扩展中的表达研究将通过实验解决 上述假设。这些研究将集中在ABD的重要性上- B类HOX基因在中肠末端构型中的作用 后肠。将对中胚层和内胚层进行比较 特定HOX基因(第13个平行对数)在大体和大体形态中的作用 后路的显微形态和细胞分化 肠道的区域。研究的目的是阐明潜在的 这些HOX基因与候选因子(如Wnt5a、CDxA)的相互作用 并特别关注于了解它们在EM信号中的作用 在肠道发育方面。所包括的研究旨在确定 肠道中HOX基因功能的区域性内脏间充质特异性 发展。

DESCRIPTION (adapted from investigator's abstract): This proposal outlines the use of the chick gastrointestinal tract (gut) as a model system to study the molecular controls of visceral development. The gut is formed by invaginations at both anterior and posterior embryonic poles. Subsequent elongation, folding and cellular differentiation result in a closed tube with gross morphological and functional distinctions along the anterior/posterior (AP) axis. This AP axis is regionalized to form the adult gut morphology of a fore-, and mid- and hind-gut Endoderm/mesoderm (EM) signals are essential in both the initiation and morphogenesis of gut tube development and in forming gut derivatives (e.g. pancreas and lung). This proposal addresses the molecular controls of the AP gut pattern. Several homologs of regulatory genes in Drosophila gut development are expressed in the vertebrate gut in patterns indicative of potential functional conservation, including the Hox genes. Specific Aims are designed to study this hypothesis: Hox genes play a key regulatory role in setting up the gross, microscopic, and molecular pattern of the vertebrate gut. Exploiting the facility of the chick system, virally mediated mis- expression studies in ovo and in organ expands will experimentally address the above hypothesis. The studies will focus on the importance of the Abd- B class of Hox genes in their role in patterning the distal mid-gut and hind-gut. Comparison will be made of the mesodermal versus endodermal roles of specific Hox genes (the 13th paralog) in patterning the gross and microscopic morphology and cellular differentiation of the posterior region of the gut. Studies are designed to elucidate potential interactions of these Hox genes and candidate factors (e.g. Wnt5a CdxA) and are specifically focused on understanding their role in EM signaling in gut development. Included are studies designed to determine the regional splanchnic mesenchymal specificity of Hox gene function in gut development.