生物
细胞生物学
内细胞团
胚胎
胚泡
河马信号通路
节点信号
祖细胞
遗传学
效应器
胚胎干细胞
胚胎发生
基因
干细胞
原肠化
作者
Claudia Gerri,Afshan McCarthy,Gregorio Alanis-Lobato,Andrej Demtschenko,Alexandre Bruneau,Sophie Loubersac,Norah M. E. Fogarty,Daniel J. Hampshire,Kay Elder,Phil Snell,Leila Christie,Laurent David,Hilde Van De Velde,Ali A. Fouladi-Nashta,Kathy K. Niakan
出处
期刊:Nature
[Springer Nature]
日期:2020-09-23
卷期号:587 (7834): 443-447
被引量:124
标识
DOI:10.1038/s41586-020-2759-x
摘要
Current understandings of cell specification in early mammalian pre-implantation development are based mainly on mouse studies. The first lineage differentiation event occurs at the morula stage, with outer cells initiating a trophectoderm (TE) placental progenitor program. The inner cell mass arises from inner cells during subsequent developmental stages and comprises precursor cells of the embryo proper and yolk sac1. Recent gene-expression analyses suggest that the mechanisms that regulate early lineage specification in the mouse may differ in other mammals, including human2-5 and cow6. Here we show the evolutionary conservation of a molecular cascade that initiates TE segregation in human, cow and mouse embryos. At the morula stage, outer cells acquire an apical-basal cell polarity, with expression of atypical protein kinase C (aPKC) at the contact-free domain, nuclear expression of Hippo signalling pathway effectors and restricted expression of TE-associated factors such as GATA3, which suggests initiation of a TE program. Furthermore, we demonstrate that inhibition of aPKC by small-molecule pharmacological modulation or Trim-Away protein depletion impairs TE initiation at the morula stage. Our comparative embryology analysis provides insights into early lineage specification and suggests that a similar mechanism initiates a TE program in human, cow and mouse embryos.
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