Contributions of VENT cells to the GI tract

VENT 细胞对胃肠道的贡献

• 批准号: 6575997
• 负责人: GURKIRPAL S SOHAL
• 金额: $ 31.52万
• 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 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6575997
• 关键词: cell population study; cell type; chick embryo; congenital gastrointestinal disorder; developmental neurobiology; gastrointestinal system; histogenesis; neural crest; neural plate /tube; neurogenesis; neuroregulation; nonmammalian vertebrate embryology

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：本研究的长期目标是了解控制胃肠道形态发生的机制和胃肠道畸形的潜在原因。在目前的观点中，神经嵴细胞是唯一的神经管来源细胞，通过形成肠神经系统（ENS）来促进胃肠道的发育。然而，我们的初步结果表明，迄今为止未被识别的神经管来源的细胞群体也有助于前肠ENS和非神经细胞的发育。这些细胞被称为腹侧移行神经管（VENT）细胞，起源于后脑的腹侧部分，并与迷走神经一起在前肠定居。几个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有特殊的贡献。这一假设将在禽类胚胎中进行验证，通过显微外科组织移植、绒毛膜-尿囊膜移植、免疫细胞化学、原位杂交和电子显微镜来确定VENT细胞的特定命运和能力。具体目的是：(1)确定VENT细胞对前肠ENS的特定衍生物和相对贡献。(2)测定前肠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的神经或非神经命运。(4)确定VENT细胞能否在中肠定植并形成ENS。(5)确定VENT细胞能否在后肠产生ENS。(6)确定来自不适当区域的VENT细胞是否能够形成ens。本研究的结果应该提供重要的新信息，表明额外的神经管来源细胞群对胃肠道发育的具体贡献和能力，这可能会导致我们对目前的一个概念的修订，即神经嵴细胞是唯一的神经管来源细胞促进胃肠道的发育。结果也可能有助于了解一些胃肠道畸形的原因，如先天性巨结肠病。