Our understanding of the molecular events driving cell specification in early mammalian development relies mainly on mouse studies, and it remains unclear whether these mechanisms are conserved across mammals, including humans. We have recently shown that the establishment of cell polarity via aPKC is a conserved event in the initiation of the trophectoderm (TE) placental program in mouse, cow, and human embryos. However, the molecular mechanisms transducing cell polarity into cell fate in cow and human embryos is unknown. Here, we have examined the evolutionary conservation of the molecular cascade downstream of aPKC in four different mammalian species: mouse, rat, cow, and human. Surprisingly, by morphokinetic and immunofluorescence analyses, we observe that rat embryos more closely recapitulate human and cow developmental dynamics, in comparison to the mouse. Nevertheless, in all four species, inhibition of the Hippo pathway by targeting LATS kinases is sufficient to drive ectopic TE initiation and downregulation of SOX2, a marker of the inner cell mass. Our comparative embryology approach uncovered intriguing differences as well as similarities in a fundamental developmental process among mammals, reinforcing the importance of cross-species investigations.
Our understanding of the molecular events driving cell specification in early mammalian development relies mainly on mouse studies, and it remains unclear whether these mechanisms are conserved across mammals, including humans. We have shown that the establishment of cell polarity via aPKC is a conserved event in the initiation of the trophectoderm (TE) placental program in mouse, cow, and human embryos. However, the mechanisms transducing cell polarity into cell fate in cow and human embryos are unknown. Here, we have examined the evolutionary conservation of Hippo signalling, which is thought to function downstream of aPKC activity, in four different mammalian species: mouse, rat, cow, and human. In all four species, inhibition of the Hippo pathway by targeting LATS kinases is sufficient to drive ectopic TE initiation and downregulation of SOX2. However, the timing and localisation of molecular markers differs across species with rat embryos more closely recapitulating human and cow developmental dynamics, compared to the mouse. Our comparative embryology approach uncovered intriguing differences as well as similarities in a fundamental developmental process among mammals, reinforcing the importance of cross-species investigations.
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