HILDE VAN DE VELDE

Human preimplantation development starts with the fertilization of an oocyte which results in a totipotent zygote. Following fertilization, the zygote undergoes a number of cleavage divisions leading to compaction on day 4 and blastulation on day 5. Compaction is a process during which the cell-cell contacts increase. The cells also acquire apical/basal polarity. A blastocyst is composed of an outer epithelial layer of cells called the trophectoderm (TE) that encloses a fluid-filled cavity with a clump of undifferentiated cells called the inner cell mass (ICM). These two cell types represent the first differentiation during early human embryogenesis. The TE forms extra-embryonic trophoblast structures and is responsible for implantation. The ICM forms the embryo proper and is the source of human embryonic stem cells (hESCs).

Due to the scarcity of human research materials and the ethical objections regarding the use of human embryos, it remains largely unknown how these lineages are established in the human. In mice, lineage segregation is controlled by specific transcription factors and several models have been described to explain how apparently morphologically identical cells differentiate into these distinct cell types. Moreover, it has recently been demonstrated that different signalling pathways play a key role during this differentiation event.

In this project we aim to analyse transcription factors (NANOG, POU5F1, SOX2 and CDX2) and signalling pathways (WNT, BMP4, Hippo) that contribute to the first lineage differentiation in human embryos. We are also investigating models such as polarisation and the position of the cells during compaction. This study will contribute to our basic knowledge on human embryogenesis and stem cell biology.