PATTERN FORMATION IN THE VERTEBRATE GUT

脊椎动物肠道中的模式形成

• 批准号: 2628391
• 负责人: DRUCILLA J ROBERTS
• 金额: $ 11.85万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2628391
• 关键词: biological signal transduction; cell cell interaction; chick embryo; developmental genetics; embryo /fetus culture; endoderm; gastrointestinal system; gel electrophoresis; gene expression; gene interaction; genetic regulation; histogenesis; homeobox genes; immunocytochemistry; in situ hybridization; mesoderm; mixed tissue /cell culture; molecular biology; organ culture; polymerase chain reaction; vertebrate embryology

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.

描述（改编自研究者摘要）：本提案概述了 使用鸡的胃肠道作为模型系统， 研究内脏发育的分子控制。肠道是由 在胚胎的前极和后极的内陷。后续 伸长、折叠和细胞分化导致封闭管 沿着沿着 前/后（AP）轴。该AP轴被区域化以形成 前肠、中肠和后肠内胚层/中胚层的成虫肠道形态 (EM)信号在肠道的启动和形态发生中是必不可少的 管发育和形成肠衍生物（例如胰腺和肺）。 该提案涉及AP肠道模式的分子控制。 果蝇肠道发育调控基因的几个同源物， 在脊椎动物肠道中表达的模式指示潜在的 功能保守，包括Hox基因。具体的目标是 旨在研究这一假设：Hox基因在以下方面发挥关键调控作用： 建立脊椎动物的宏观、微观和分子模式 直觉利用鸡系统的便利性，病毒介导的mis- 在卵和器官扩展中的表达研究将实验性地解决 上述假设。这些研究将集中在Abd的重要性- B类Hox基因在形成远端中肠和 后肠将中胚层与内胚层进行比较 特定的Hox基因（第13部分）在图案化的总和 显微形态学和细胞分化的后部 肠道区域。研究旨在阐明潜在的 这些Hox基因和候选因子（例如Wnt 5a CdxA）的相互作用 并特别关注它们在EM信号中的作用， 在肠道发育中。包括旨在确定 Hox基因在肠道中功能的局部内脏间充质特异性 发展