CELL GROWTH AND DIFFERENTIATION IN THE VERTEBRATE EMBRYO

说明(改编自《调查员摘要》)： 原肠形成是一个基本的发育过程，在小鼠体内 它协调复杂的细胞和组织运动与细胞生长和 增殖以重组和分化胚胎外胚层 进入确定的外胚层、中胚层和内胚层胚层。 胎儿。指导原肠形成的遗传途径才刚刚开始 在小鼠中通过靶向和随机突变而解体 鱼。耐人寻味的是，一些原肠胚阶段的小鼠突变体 是通过对已知基因的定向破坏而被发现的， 通过他们与人类疾病的接触，参与 增殖、分化和信号的基本细胞过程 转导。最近的例子包括成纤维细胞生长因子 受体(FGFR-1)、BRCA1、BRCA2、亨廷顿病同系物(HDH)、 和肿瘤抑制基因Smad4/Dpc4。因此，对小说的研究 原肠胚阶段的小鼠突变很可能导致鉴定 在细胞协调中起关键作用的基因 生长、增殖和分化。这项提案的主题是 是一种隐性的转基因插入突变， 打乱了中间条纹的组装，这部分 形成非轴向胚胎中胚层的原始条纹，如 体细胞中胚层。这一新的表型揭示了 中间条纹是由一条以前未知的途径介导的，这条途径 在基因上可以与那些指挥形成的人分开 近端和远端条纹区域的规格。因此，a AMN基因座的突变基因在这一途径中肯定起着关键作用。 嵌合体分析表明，这种基因，amn基因，在 内脏内胚层引导中纹的形成和 因此，AMN为内脏内胚层定义了一个新的角色 原肠形成。这项提议的主要目标是 克隆amn基因。

DESCRIPTION (Adapted from the Investigator's Abstract): Gastrulation is a fundamental developmental process, and in the mouse it coordinates complex cell and tissue movements with cell growth and proliferation to reorganize and differentiate the embryonic ectoderm into the definitive ectoderm, mesoderm, and endoderm germ layers of the fetus. The genetic pathways directing gastrulation are only beginning to be unraveled by both targeted and random mutagenesis in the mouse and fish. Intriguingly, a number of gastrulation stage mouse mutants have been discovered through the targeted disruption of genes that are known, through their involvement with human disease, to participate in the basic cellular processes of proliferation, differentiation, and signal transduction. Recent examples include the fibroblast growth factor receptor (Fgfr-1), Brca1, Brca2, Huntington's disease homologue (Hdh), and the tumor suppressor Smad4/Dpc4. Thus the study of novel gastrulation stage mouse mutants is likely to lead to the identification of genes that serve pivotal functions in the coordination of cell growth, proliferation, and differentiation. The subject of this proposal is amnionless (amn), a recessive transgene insertional mutation that disrupts the assembly of the middle streak, this portion of the primitive streak that gives rise to non-axial embryonic mesoderm, such as somitic mesoderm. This novel phenotype reveals that the formation of the middle streak is mediated by a previously unknown pathway, one that is genetically separable from those directing the formation and specification of the proximal and distal streak regions. Therefore, a disrupted gene at the amn locus must play a key role in this pathway. Chimera analyses have shown that this gene, the amn gene, functions in the visceral endoderm to direct the formation of the middle streak and thus, that amn defines a new role for the visceral endoderm during gastrulation. The primary objective of this proposal is to positionally clone the amn gene.