Wnt signaling regulation during early mammalian lineaje segregation.

One of the initial steps of embryo development in mammals, before the embryo implantation in the uterus, consists in the segregation and establishment of the Epiblast (Epi) and Primitive Endoderm (PrEn) cell lineages derived from the Inner Cell Mass (ICM) of the blastocysts. Defects in Epi vs. PrEn segregation affect embryo development and result in embryonic malformation and early embryo lethality. Our knowledge about the differentiation and establishment of the Epi and PrEn lineages is very limited. We have recently developed a new strategy to culture Epi and PrEn precursors in vitro in which the biological and functional characteristics of their in vivo counterparts are maintained. In this project proposal, we aim to elucidate the crucial signalling pathways and key downstream effectors implicated in the Epi vs. PrEn segregation, using both in vitro and in vivo systems. We have identified the canonical Wnt pathway as a putative modulator of this initial steps of lineage segregation. We aim to further investigate the role of Wnt signalling and its downstream effectors, the Tcf/Lef family members, during the Epi vs. PrEn segregation and maintenance. The identification of signalling pathways and transcription factors involved in the embryonic and extraembryonic tissue formation will be extremely valuable to shed light on the mechanisms of mammalian development and may be conducive to prevent embryonic defects.