期刊
NATURE
卷 587, 期 7834, 页码 443-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41586-020-2759-x
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资金
- MSD
- Fonds Wetenschappelijk Onderzoek Flanders [FWOAL722]
- Wetenschappelijk Fonds Willy Gepts (WFWG, UZ Brussel) [G142]
- Comparative Biomedical Sciences Departmental fund from the Royal Veterinary College
- Francis Crick Institute from Cancer Research UK [FC001120]
- UK Medical Research Council [FC001120]
- Wellcome Trust [FC001120]
- Rosa Beddington Fund
Comparative analysis of human, cow and mouse embryos shows that a mechanism involving atypical protein kinase C initiates the trophectoderm program during the morula stage in these three species. 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 sac(1). Recent gene-expression analyses suggest that the mechanisms that regulate early lineage specification in the mouse may differ in other mammals, including human(2-5)and cow(6). 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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