May 3, 2019

Sergio Menchero

14.45-15.00 Sergio Menchero

‘Notch drives transitions in cell potency during mouse preimplantation development’

The onset of cell differentiation in the mammalian embryo entails the loss of totipotency to favor the appearance of the first lineage-committed cell populations. The Notch signalling pathway plays fundamental roles in diverse developmental processes in metazoans, where it is important in driving cell fate and directing differentiation of various cell types. However, we still have limited knowledge about the role of Notch in early preimplantation stages of mammalian development. We have previously shown that the Notch pathway cooperates with Hippo in the regulation of Cdx2, key element in the trophectoderm lineage. Now, by using genetic and pharmacological tools in vivo, together with image analysis of single embryos, we have found that Notch is active from the 4-cell stage. Transcriptomic analysis in single morula identified novel Notch targets, such as early naïve pluripotency markers or transcriptional repressors such as TLE4. These findings suggest that Notch is triggering the gradual loss of potency that takes place in the early mouse embryo prior to the specification of the first lineages.