CELL GROWTH AND DIFFERENTIATION IN THE VERTEBRATE EMBRYO

描述（改编自研究者摘要）： 在小鼠中， 它协调复杂的细胞和组织运动与细胞生长 增殖重组分化胚胎外胚层 进入的最终外胚层，中胚层，和内胚层的胚层， 胎儿引导原肠胚形成的遗传途径才刚刚开始 通过小鼠中的靶向和随机诱变来解开， 鱼.有趣的是，一些原肠胚形成阶段的小鼠突变体 是通过对已知基因的定向破坏而发现的， 通过参与人类疾病的研究， 增殖、分化和信号传导的基本细胞过程 转导最近的例子包括成纤维细胞生长因子 受体（Fgfr-1），Brca 1，Brca 2，亨廷顿病同源物（Hdh）， 和肿瘤抑制因子Smad 4/Dpc 4。因此，小说研究 原肠胚形成阶段小鼠突变体可能导致鉴定 在细胞协调中起关键作用的基因 生长、增殖和分化。本提案的主题 是一种隐性转基因插入突变， 破坏了中间条纹的组装， 产生非轴向胚胎中胚层的原始条纹，如 体细胞中胚层。这种新的表型表明， 中间的条纹是由一种以前未知的途径介导的， 从基因上来说，与那些指导形成的人是分开的， 近端和远端条纹区域的规格。因此 amn基因座上被破坏的基因在该途径中一定起关键作用。 嵌合体分析表明，这个基因，amn基因，功能在 内脏内胚层引导中间条的形成， 因此，amn为内脏内胚层定义了一个新的角色， 原肠胚形成本提案的主要目的是从立场上 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.