PhD Researcher Max Planck Institute for Molecular Biomedicine, Germany
Abstract: Primordial germ cells (PGCs) are the precursors that develop into sperm and eggs. In mice, around embryonic day (E) 6.25, a small group of epiblast cells adopt germ cell fate and segregate from the epiblast. Studying the segregation of PGCs from the epiblast has been challenging due to technical limitations.
In this study, we employed a 3D embryonic stem cell-based in vitro culture system and direct embryo analysis to investigate the morphogenetic changes that drive PGC segregation from the epiblast. We found that the newly specified PGCs undergo dramatic shape changes following their specification at the boundary between the epiblast and extraembryonic ectoderm (ExE). To understand the mechanism behind PGC segregation, we first examined and ruled out the possibility of Epithelial-Mesenchymal Transition (EMT). We then analyzed the morphological changes in PGCs during early segregation using PGC reporter mouse embryos and the 3D in vitro model in combination with transcriptional analysis. We discovered that as PGCs reacquire naïve pluripotency, they lose epithelial polarity and this allows them to segregate from the epiblast. Additionally, our findings suggest a role of small GTPases downstream of naïve pluripotency factors in orchestrating epithelial morphogenesis during PGC delamination.
Altogether, this study provides new insights into the cellular and molecular mechanisms underlying PGC segregation, broadening the fundamental understanding of early germ cell development.
