TY - JOUR
T1 - Initiation of a conserved trophectoderm program in human, cow and mouse embryos
AU - Gerri, Claudia
AU - McCarthy, Afshan
AU - Alanis-Lobato, Gregorio
AU - Demtschenko, Andrej
AU - Bruneau, Alexandre
AU - Loubersac, Sophie
AU - Fogarty, Norah M E
AU - Hampshire, Daniel
AU - Elder, Kay
AU - Snell, Phil
AU - Christie, Leila
AU - David, Laurent
AU - Van de Velde, Hilde
AU - Fouladi-Nashta, Ali A
AU - Niakan, Kathy K
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85091354657&partnerID=8YFLogxK
U2 - 10.1038/s41586-020-2759-x
DO - 10.1038/s41586-020-2759-x
M3 - Article
C2 - 32968278
VL - 587
SP - 443
EP - 447
JO - Nature
JF - Nature
SN - 1476-4687
IS - 7834
ER -