ABSTRACT
Primordial germ cells (PGCs) are the precursor of the gametes. They are specified in the early post-implantation embryo and go through a complex genome-wide transcriptional dynamics and tightly regulated epigenetic reprogramming. The knowledge of this process is important because defects during germ cell formation could entail infertility problems.
In mammals PGCs formation is conducted by epigenesis. A small founder population placed in the posterior-proximal epiblast receives the necessary inductive signals (BMP, SMAD, WNT, NODAL) to do so. This population undergoes repression of somatic genes and reacquisition of pluripotency, which is triggered in mouse by PRDM1 and in human by SOX17, in collaboration with other factors (PRDM14, AP2ϒ, LIN28). In addition, PGC go through a drastic wave of DNA demethylation (with participation of active and passive mechanisms) that affects even imprinted genes and repetitive elements, with the aim to remove the differential parental marks. Later these marks will be replaced by specific marks depending of the sex of the embryo. Nonetheless, specific methylated loci escape demethylation and could participate in transgenerational epigenetic inheritance. Histone modifications also suffer reorganization, following similar dynamics in mouse and human. Mouse and human PGCs show similarities and differences (regarding morphogenesis) that are explored along this chapter.
