The glial cells missing-1 protein is essential for branching morphogenesis in the chorioallantoic placenta
The glial cells missing-1 protein is essential for branching morphogenesis in the chorioallantoic placenta
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DOI：
10.1038/77076
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发表时间：
2000-07-01
期刊：
影响因子：
30.8
通讯作者：
Cross, JC
中科院分区：
文献类型：
--
作者：
Anson-Cartwright, L;Dawson, K;Cross, JC
胎盘的滋养层细胞在胚泡阶段形成，并在着床后分化为专门的亚型（1，2）。在小鼠中，胎盘的外层由滋养层巨细胞组成，滋养层巨细胞侵入子宫并通过产生具有血管生成（3）和血管舒张（4）作用的细胞因子促进母体血液流向着床部位。最内层称为迷路，由分支绒毛组成，为营养运输提供了大的表面积，并由滋养层细胞和来自尿囊的中胚层细胞组成。胚龄（E）8.5天后，绒毛尿囊绒毛通过最初平坦的滋养层细胞（绒毛板）的广泛折叠和分支发育，以响应与尿囊的接触。我们在这里显示Gcm 1。编码转录因子神经胶质细胞缺失-1（Gcm 1）。在绒毛膜扁平板阶段的绒毛膜滋养层细胞的小簇中以及在形态发生开始时绒毛膜尿囊折叠和延伸的位点处表达。小鼠Gcm 1突变导致绒毛膜尿囊界面分支完全阻断，导致E10时由于胎盘迷路缺失导致胚胎死亡。此外，绒毛膜滋养层细胞在Gcm 1缺陷的胎盘不融合形成合体滋养层。胎盘绒毛的异常发育经常与人类胎儿死亡和宫内生长受限相关，我们的研究提供了对胎盘发育这方面的最早分子见解。
Trophoblast cells of the placenta are established at the blastocyst stage and differentiate into specialized subtypes after implantation(1,2). In mice, the outer layer of the placenta consists of trophoblast giant cells that invade the uterus and promote maternal blood flow to the implantation site by producing cytokines with angiogenic(3) and vasodilatory(4) actions. The innermost layer, called the labyrinth, consists of branched villi that provide a large surface area for nutrient transport and are composed of trophoblast cells and underlying mesodermal cells derived from the allantois. The chorioallantoic villi develop after embryonic day (E) 8.5 through extensive folding and branching of an initially flat sheet of trophoblast cells, the chorionic plate, in response to contact with the allantois. We show here that Gcm1. encoding the transcription factor glial cells missing-1 (Gcm1). is expressed in small clusters of chorionic trophoblast cells at the flat chorionic plate stage and at sites of chorioallantoic folding and extension when morphogenesis begins. Mutation of Gcm1 in mice causes a complete block to branching of the chorioallantoic interface, resulting in embryonic mortality by E10 due to the absence of the placental labyrinth. In addition, chorionic trophoblast cells in Gcm1-deficient placentas do not fuse to form syncytiotrophoblast. Abnormal development of placental villi is frequently associated with fetal death and intrauterine growth restriction in humans, and our studies provide the earliest molecular insight into this aspect of placental development.