DIFFERENTIATION AND MORPHOGENESIS OF EXTRAEMBRYONIC MESODERM

哺乳动物胚胎的早期发育产生了胚外细胞 提供营养和物质环境的世系 胚胎存活。项目VI的重点是开发 胚外中胚层，形成的三种胚外组织之一 在植入的围产期。与滋养层细胞和 胚外内胚层谱系，分化为单细胞 着床前的几层，胚外中胚层在 原肠形成。原肠形成是一个复杂的形态发生过程，包括 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。 该项目以前的结果强烈地牵涉到胚胎外 中胚层在孤雌胚胎围着床期死亡中的作用 与绒毛尿囊融合失败有关。本研究的重点是 胚外中胚层的起源、分化和形态发生 因为人们对这种哺乳动物原肠作用的产物知之甚少。这个 项目一开始就分析了中胚层诱导的机制 多肽生长因子在围着床期胚胎和多能细胞中的表达 (目标1)，继续分析特定转录的作用 胚外中胚层的分子决定因素 区分(目标2)，然后将这些发现与分析相结合 在胚胎外的决定和其他形态发生功能 中胚层发育(目标3)。需要检验的假设是 原肠形成早期的诱导事件足以说明 胚外中胚层命运。为了解决这个问题，在体外 将研究外植体的上胚层，以评估 多肽生长因子--相当于小鼠的两栖动物帽子 功能获得和功能丧失的遗传转化 胚胎和多能胚胎来源细胞将被用来评估 特定生长因子的作用；中胚层细胞的移植 胚胎之间的距离将被用来评估它们的决定状态。 总的来说，这些研究结合了小鼠胚胎的遗传强度 用两栖类实验方法系统来理解 绒毛尿囊膜胎盘的这一重要组成部分的发育。 这些结果将对上的计划主题做出整体贡献 植入，并将对人类健康产生重大好处，包括 不孕症及其早期证候认识的意义 妊娠丢失和产生的胚胎的低效着床率 通过医疗辅助受孕。

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.