Onderzoek Naar De Mechanismen Van Primitief Endoderm Specificatie: Een Odyssee Van Het Lot

Around 30% of human pregnancies fail at the early stages of embryo development when cell lineages need to be correctly established. During the pre-implantation stage of the blastocyst , the cells of the Inner Cell Mass (ICM), segregate and commit to the the Epiblast (Epi) and Primitive Endoderm (PrEn) cell lineages. Defects in Epi vs. PrEn segregation affect embryo development and result in embryonicmalformation 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 which maintain the biological and functional characteristics of their counterparts in vivo. In this project proposal, we aim to elucidate the crucial signalling pathways and key downstream genes implicated in the Epi vs. PrEn segregation, using both in vitro and in vivo systems. We have already identified the canonical Wnt pathway as a putative modulator of the 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, differentiation and establishment. 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 highly conducive to prevent embryonic defects.