Initiation of a conserved trophectoderm program in human, cow and mouse embryos.
Nature, 2020/11;587(7834):443-447.
Gerri C[1], McCarthy A[1], Alanis-Lobato G[1], Demtschenko A[2], Bruneau A[3], Loubersac S[3, 4], Fogarty NME[1, 5], Hampshire D[6], Elder K[7], Snell P[7], Christie L[7], David L[3, 8], Van de Velde H[2, 9], Fouladi-Nashta AA[6], Niakan KK[10, 11]
Affiliations
PMID: 32968278DOI: 10.1038/s41586-020-2759-x
Impact factor: 69.504
Abstract
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.
MeSH terms
Adaptor Proteins, Signal Transducing; Animals; Biological Evolution; Blastocyst Inner Cell Mass; Cattle; Cell Lineage; Cell Polarity; Ectoderm; Embryo, Mammalian; Female; GATA3 Transcription Factor; Gene Expression Regulation, Developmental; Hippo Signaling Pathway; Humans; Mice; Morula; Placenta; Pregnancy; Protein Kinase C; Protein Serine-Threonine Kinases; SOXB1 Transcription Factors; Signal Transduction; Transcription Factors; Transcription, Genetic; Trophoblasts; YAP-Signaling Proteins; Yolk Sac
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