PLAC1 in Placental Development

描述（由申请人提供）：本提案的目的是确定PLAC 1（一种新的滋养层特异性X连锁基因）在胎盘和胎儿发育中的功能作用。PLAC 1在胎盘发育中的重要作用是由其组织特异性和时间表达模式强烈建议的。这是加强了胎儿生长迟缓表型和胎盘生长异常相关的X染色体缺失的区域中的PLAC 1映射。由于X染色体的这一区域缺乏基因，PLAC 1是导致观察到的表型的主要候选基因。PLAC 1与透明质酸蛋白3（ZP 3）具有序列同源性，表明其可能参与母胎界面处的特异性细胞相互作用，可能充当细胞表面受体。总体来看，这些观察结果表明，PLAC 1编码的胎盘特异性蛋白质的重要性哺乳动物生殖。初步的证据表明，在滋养细胞分化过程中，PLAC 1的表达显著上调，并仅限于分化的合体滋养细胞和绒毛膜层滋养细胞。所提出的研究将有助于确定的作用，PLAC 1/PLAC 1在胎盘生长的追求以下目标：首先，PLAC 1多肽的特点，生化，其亚细胞定位在正常滋养层的定义。将确定对其功能重要的特定蛋白质-蛋白质相互作用。第二，Plac在胎盘和胚胎生长中的作用将在小鼠突变模型中在整个动物水平上进行研究。鉴于PLAC 1/PLAC 1表达的限制性性质，这些研究可能会为胎盘和胎儿发育中重要的机制提供新的见解。

DESCRIPTION (provided by applicant): The objective of this proposal is to determine the functional role of PLAC1, a novel trophoblast-specific and X-linked gene, in placental and fetal development. A significant role for PLAC1 in placental development is strongly suggested by its tissue-specific and temporal patterns of expression. This is strengthened by a fetal growth retardation phenotype and placental growth abnormalities associated with X chromosome deletions in the region to which PLAC1 maps. Because of a paucity of genes in this region of the X-chromosome, PLAC1 is the leading candidate gene responsible for the observed phenotype. PLAC1 shares sequence homology with the zona pellucida protein 3 (ZP3) suggesting it may be involved in specific cellular interactions at the maternal-fetal interface, possibly acting as a cell surface receptor. Viewed collectively, these observations suggest that PLAC1 encodes a placenta-specific protein of importance to mammalian reproduction. Preliminary evidence suggests that PLAC1 expression is markedly upregulated during trophoblast differentiation and limited to the differentiated syncytiotrophoblast and trophoblasts of the chorion laeve. The proposed studies will help define the role of PLAC1/Plac1 in placental growth by pursuing the following aims: First, the PLAC1 polypeptide will be characterized, biochemically, and its subcellular localization in the normal trophoblast defined. Specific protein-protein interactions important to its function will be identified. Second, the role of Plac in placental and embryonic growth will be studied at the whole animal level in a mouse mutant model. Given the restricted nature of PLAC1/Plac1 expression, these studies will likely provide novel insights into mechanisms important in placental and fetal development.