Cell Growth and Differentiation in the Vetebrate Embryo

描述(申请人提供)：小鼠原肠胚的定义特征 是原始条纹，一种外胚层细胞穿过的动态结构 进入以产生新生的中胚层和内胚层。命运地图的研究已经 揭示了原始条纹可以分为三种功能 区域：形成生殖细胞和胚胎外细胞的近端条纹 中胚层；产生心脏中胚层和结节来源的远端条纹 轴向中胚层；产生非中线主干的中线条纹 中胚层。小鼠突变羊膜(AMN)不仅损害了外胚层的生长， 而且还特别破坏了中间部分的组装和/或功能 原始的条纹。最近对amn基因的鉴定表明，它 编码一种新的I型跨膜蛋白，该蛋白在 原肠发育过程中的内脏内胚层。因此，AMN必须扮演细胞角色 内脏内膜非自主调节外胚层细胞行为 生长和中间原始条纹的规格所必需的。这个 AMN的胞外区含有一个类似的富含半胱氨酸(CR)的基序 与蛋白质中BMP结合的CR模块，如Chordin，已知起到 BMP信号的调制器。这些发现表明，Amn可能会指导 上胚层生长和中条纹干中胚层的产生 在内脏内胚层中调节BMP信号通路。 这种工作模式将通过生物化学、生物化学、 在培养的哺乳动物细胞、小鼠、非洲爪哇、 还有果蝇。此外，上胚层细胞行为(S)由 内脏内胚层的“AMN通路”将通过克隆鉴定。 谱系分析和靶向转基因表达。耐人寻味的是，另外两个 已知的Amn表达部位，肾脏近端小管和肠，类似于 内脏内胚层，极化上皮，专门分泌和 再吸收。在人类和果蝇中发现的AMN同源物表明 Amn很可能在进化中扮演着保守的角色， 分化，或这些特化细胞类型的功能，通常是 人类疾病。

DESCRIPTION (provided by applicant): The defining feature of the mouse gastrula is the primitive streak, a dynamic structure through which epiblast cells ingress to generate nascent mesoderm and endoderm. Fate mapping studies have revealed that the primitive streak can be divided into three functional regions: the proximal streak that gives rise to germ cells and extraembryonic mesoderm; the distal streak that generates cardiac mesoderm and node-derived axial mesendoderm; and the middle streak that produces non-midline trunk mesoderm. The mouse mutation amnionless (amn) not only impairs epiblast growth, but also specifically disrupts the assembly and/or function of the middle primitive streak. The recent identification of the Amn gene shows that it encodes a novel type I transmembrane protein that is specifically expressed in the visceral endoderm during gastrulation. Thus Amn must act cell non-autonomously in the visceral endodemi to govern epiblast cell behaviors required for growth and the specification of the middle primitive streak. The extracellular region of Amn includes a cysteine rich (CR) motif with similarity to BMP-binding CR modules in proteins, such as Chordin, known to act as modulators of BMP signaling. These findings suggest that Amn may direct epiblast growth and the production of middle streak-derived trunk mesoderm by acting to modulate a BMP signaling pathway in the underlying visceral endoderm. This working model will be explored though a combination of biochemical, genetic, and embryological studies in cultured mammalian cells, mice, Xenopus, and Drosophila. In addition, the epiblast cell behavior(s) controlled by the "Amn pathway" in the visceral endoderm will be identified through a clonal lineage analysis and targeted transgene expression. Intriguingly, the two other known sites of Amn expression, kidney proximal tubule and intestine, are, like the visceral endoderm, polarized epithelia specialized for secretion and resorption. The finding of Amn homologues in both human and Drosophila indicate the Amn likely plays an evolutionarily conserved role in the development, differentiation, or function of these specialized cell types, often targets of human disease.