PLAC1 in Placental Development

描述（由申请人提供）：本提案的目的是确定PLAC1（一种新的滋养细胞特异性和x连锁基因）在胎盘和胎儿发育中的功能作用。PLAC1的组织特异性和时间表达模式强烈提示其在胎盘发育中的重要作用。胎儿生长迟缓表型和胎盘生长异常与PLAC1所在区域的X染色体缺失有关，这一点得到了加强。由于在x染色体的这一区域缺乏基因，PLAC1是负责观察到的表型的主要候选基因。PLAC1与透明带蛋白3 （ZP3）具有序列同源性，提示其可能参与母胎界面的特定细胞相互作用，可能作为细胞表面受体。综上所述，这些观察结果表明，PLAC1编码一种对哺乳动物生殖具有重要意义的胎盘特异性蛋白。初步证据表明，在滋养细胞分化过程中，PLAC1的表达明显上调，且仅限于已分化的合体滋养细胞和绒毛膜滋养细胞。拟开展的研究将通过以下目标来帮助确定PLAC1/ PLAC1在胎盘生长中的作用：首先，将对PLAC1多肽进行生物化学表征，并确定其在正常滋养细胞中的亚细胞定位。将确定对其功能重要的特定蛋白质-蛋白质相互作用。其次，将在小鼠突变模型的全动物水平上研究place在胎盘和胚胎生长中的作用。考虑到PLAC1/ PLAC1表达的有限性，这些研究可能会为胎盘和胎儿发育的重要机制提供新的见解。

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.