Contributions of VENT cells to the GI tract

VENT 细胞对胃肠道的贡献

• 批准号: 7163060
• 负责人: GURKIRPAL S SOHAL
• 金额: $ 29.83万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7163060
• 关键词: Authorization documentation; Birds; Cells; Cephalic; Chick Embryo; Cities; Congenital Megacolon; Cranial Nerves; Development; Disclosure; Dorsal; Duodenum; Electron Microscopy; Embryo; Emigrations; Endoderm; Enteric Nervous System; Epithelial Cells; Face; Failure; Gastrointestinal tract structure; Goals; Hindgut; Human Resources; In Situ Hybridization; Instruction; Interstitial Cell of Cajal; Investigation; LacZ Genes; Last Name; Lead; Medical; Mesoderm; Mesoderm Cell; Midgut; Morphogenesis; Names; Neural Crest Cell; Neural tube; Neuroglia; Neurons; Numbers; Play; Population; Primitive foregut structure; Principal Investigator; Printing; Prospective Studies; Purpose; Relative (related person); Research Project Grants; Role; Route; Site; Smooth Muscle Myocytes; Source; Stomach; Testing; Tissue Transplantation; To specify; USA Georgia; Vagus nerve structure; Western Asia Georgia; base; chorioallantoic membrane; college; concept; gastrointestinal; hindbrain; immunocytochemistry; malformation; programs; relating to nervous system

The long-term goal of this study is to understand the mechanisms governing morphogenesis of the GI tract and the underlying causes of GI malformations. In the current view, the neural crest cells are the sole neural tube-derived cells contributing to the development of the GI tract, by forming the enteric nervous system (ENS). However, our preliminary results indicate that a heretofore unrecognized population of neural tube- derived cells also contributes to the development of the ENS and non-neural cells in the foregut. These cells, termed as the Ventrally Emigrating Neural Tube (VENT) cells, originate from the ventral part of the hindbrain, and colonize the foregut in association with the vagus nerve. Several different observations have prompted us to hypothesize that the VENT cells make specific contributions to the morphogenesis of the GI tract. The hypothesis will be tested in avian embryos by determining the specific fate and capabilities of the VENT cells by using microsurgical tissue transplantation, chorioallantoic membrane grafting, immunocytochemistry, in situ hybridization, and electron microscopy. The specific aims are to: (1) Determine the specific derivatives and relative contributions of the VENT cells to the ENS of the foregut. (2) Determine the non-neural derivatives of the VENT cells in the foregut. (3) Determine if the VENT cells are pre-specified to the neural or non-neural fate in the foregut. (4) Determine whether the VENT cells can colonize the midgut and form the ENS. (5) Determine whether the VENT cells can give rise to the ENS in the hindgut. (6) Determine whether the VENT cells from an inappropriate region are capable of forming the ENS. Results of this study should provide significant new information by indicating the specific contributions and capabilities of an additional neural tube-derived cell population to the development of the GI tract, which may lead to a revision of one our current concepts, that the neural crest cells are the sole neural tube-derived cells contributing to the development of the GI tract. Results may also help in understanding the cause of some of the GI malformations, such as the Hirschsprung's disease.

这项研究的长期目标是了解胃肠道形态发生的机制 以及胃肠道畸形的根本原因。目前看来，神经嵴细胞是唯一的神经细胞。 管源细胞通过形成肠神经系统促进胃肠道的发育 （ENS）。然而，我们的初步结果表明，迄今为止尚未认识到的神经管群体 衍生细胞还有助于前肠中 ENS 和非神经细胞的发育。这些 细胞，称为腹侧移出神经管（VENT）细胞，起源于神经管的腹侧部分。 后脑，并定居于与迷走神经相关的前肠。几种不同的观察结果 促使我们假设 VENT 细胞对胃肠道的形态发生做出特定贡献 道。该假设将通过确定鸟类胚胎的具体命运和能力来进行检验。 VENT细胞通过显微外科组织移植、绒毛尿囊膜移植、 免疫细胞化学、原位杂交和电子显微镜。 具体目标是： (1) 确定 VENT 细胞对前肠 ENS 的特定衍生物和相对贡献。 (2) 确定前肠 VENT 细胞的非神经衍生物。 (3) 确定 VENT 细胞是否预先指定为前肠中的神经或非神经命运。 (4) 确定VENT细胞能否定植中肠并形成ENS。 (5)确定VENT细胞是否可以在后肠中产生ENS。 (6) 确定来自不适当区域的VENT细胞是否能够形成ENS。 这项研究的结果应通过指出具体贡献和 额外的神经管衍生细胞群对胃肠道发育的能力，这可能 导致对我们当前概念的修订，即神经嵴细胞是唯一的神经管衍生细胞 有助于胃肠道发育的细胞。结果也可能有助于理解原因 一些胃肠道畸形，例如先天性巨结肠症。