PATTERN FORMATION IN THE VERTIBRATE GUT

脊椎动物肠道中的模式形成

• 批准号: 6181840
• 负责人: DRUCILLA J ROBERTS
• 金额: $ 12万
• 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/6181840
• 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（改编自研究者的摘要）：该提案概述了 使用小鸡胃肠道（肠道）作为模型系统 研究内脏发育的分子控制。肠道是由 胚胎前极和后极的内陷。随后的 伸长、折叠和细胞分化导致封闭管 沿线具有总体形态和功能差异 前/后（AP）轴。该 AP 轴被区域化以形成 前肠、中肠和后肠内胚层/中胚层的成体肠道形态 (EM) 信号对于肠道的启动和形态发生至关重要 管发育和形成肠道衍生物（例如胰腺和肺）。 该提案解决了 AP 肠道模式的分子控制问题。 果蝇肠道发育中调节基因的几个同源物是 在脊椎动物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 旨在研究这一假设：Hox 基因在 建立脊椎动物的总体、微观和分子模式 肠道。利用雏鸡系统的设施，病毒介导的错误 卵和器官扩展中的表达研究将通过实验解决 上述假设。研究将重点关注 Abd- B 类 Hox 基因在远端中肠和中肠模式中的作用 后肠。中胚层与内胚层的比较 特定 Hox 基因（第 13 个旁系同源物）在总体和 后部的显微形态和细胞分化 肠道区域。研究旨在阐明潜力 这些 Hox 基因与候选因子（例如 Wnt5a CdxA）的相互作用 并特别专注于了解它们在电磁信号传导中的作用 在肠道发育中。其中包括旨在确定 肠道中Hox基因功能的区域内脏间充质特异性 发展。