DIFFERENTIATION AND MORPHOGENESIS OF EXTRAEMBRYONIC MESODERM

胚外中胚层的分化和形态发生

• 批准号: 6341021
• 负责人: Roger Arnold Pedersen
• 金额: $ 18.05万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6341021
• 关键词: alleles; cell differentiation; cell type; developmental genetics; early embryonic stage; ectoderm; embryo implantation; embryonic stem cell; fibroblast growth factor; gene expression; genetic markers; growth factor receptors; human tissue; laboratory mouse; mesoderm; messenger RNA; parthenogenesis; pluripotent stem cells; transcription factor

Early development of mammalian embryos generates the extraembryonic cell lineages that provide nutritional and physical environments essential for embryonic survival. Project VI focuses on the development of extraembryonic mesoderm, one of three extraembryonic tissues formed during the peri-implantation period. Unlike trophoblast and extraembryonic endoderm lineages, which differentiate as single cell layers before implantation, extraembryonic mesoderm forms during gastrulation. Gastrulation is a complex morphogenetic process involving epithelial-mesenchymal transformation and cell migration, which transforms the epiblast layer into mesoderm, endoderm and ectoderm. Previous results of this Project strongly implicated extraembryonic mesoderm in the peri-implantation death of parthenogenetic embryos, owing to a failure of chorioallantoic fusion. The present study focuses on the origin, differentiation and morphogenesis of extraembryonic mesoderm, because this product of mammalian gastrulation is poorly understood. The Project begins by analyzing the mechanisms of mesoderm induction by peptide growth factors in peri-implantation embryos and pluripotent cells (Aim 1), continues by analyzing the roles of specific transcription factors as molecular determinants of extraembryonic mesoderm differentiation (Aim 2), and then integrates these findings with analysis of determination and other morphogenetic functions during extraembryonic mesoderm development (Aim 3). The hypothesis to be tested is that inductive events in early gastrulation are sufficient to specify an extraembryonic mesoderm fate. To approach this problem, in vitro explants of the epiblast layer will be studied to assess the effects of peptide growth factors--a mouse equivalent of the amphibian animal cap assay; gain-of-function and loss-of-function genetic transformation of embryos and pluripotent embryo-derived cells will be used to assess the role of specific growth factors; and transplantation of mesoderm cells between embryos will be used to assess their state of determination. together, these studies combine the genetic strengths of the mouse embryo system with amphibian-type experimental approaches to understand the development of this essential component of the chorioallantoic placenta. The results will contribute integrally to the Program theme on implantation and will have significant human health benefits, including implications for understanding syndromes of infertility and early pregnancy loss and inefficient implantation rates of embryos generated through medically assisted conception.

哺乳动物胚胎的早期发育产生胚外细胞 提供营养和物质环境的血统， 胚胎存活 项目六的重点是发展 胚外中胚层，形成的三种胚外组织之一 在围着床期。 与滋养层细胞不同， 胚外内胚层谱系，其分化为单细胞 在着床前，胚外中胚层形成， 原肠胚形成 原肠胚形成是一个复杂的形态发生过程， 上皮-间充质转化和细胞迁移， 将上胚层转化为中胚层、内胚层和外胚层。 该项目的先前结果强烈暗示胚外 中胚层在孤雌胚胎的围植入期死亡，由于 导致绒毛膜尿囊融合失败 本研究的重点是 胚外中胚层的起源、分化和形态发生， 因为对哺乳动物原肠胚形成的产物知之甚少。 的 项目开始分析中胚层诱导的机制， 围植入期胚胎和多能细胞中的肽生长因子 (Aim 1），继续分析特定转录的作用， 胚外中胚层的分子决定因子 区分（目标2），然后将这些发现与分析整合 决定和其他形态发生的功能 中胚层发育（Aim 3）。 有待检验的假设是， 早期原肠胚形成中的诱导事件足以说明 胚外中胚层的命运。 为了解决这个问题，在体外 将研究外胚层的外植体以评估 肽生长因子--一种相当于两栖动物帽的小鼠 功能获得性和功能丧失性遗传转化 胚胎和多能胚胎衍生细胞将用于评估 特异性生长因子的作用和中胚层细胞的移植 将用于评估它们的决定状态。 总之，这些研究联合收割机结合了小鼠胚胎的遗传优势， 系统与两栖式实验方法，以了解 绒毛膜尿囊胎盘这一重要成分的发育。 这些结果将对该方案的主题作出整体贡献， 植入，并将有显着的人类健康的好处，包括 对了解不孕症综合征和早期 妊娠丢失和胚胎植入率低 通过医学辅助受孕