Our work on these amazing cells raises exciting and important questions about adaptations in nuclear mechanics during migration in vivo, the role of DNA damage repair in early germ cell development, and even origins of genetic diversity in the germline. We hope you enjoy it!

At the same time, PGCs deplete their nuclear lamina and exhibit wrinkled nuclear envelopes – we propose that this might help them to migrate damage-free through the increasingly confining tissues of the embryo.

Further, we saw a higher incidence of DNA damage in PGCs (not any other cells) towards the later stages of migration and when we increased confinement. So PGCs are undertaking a surprisingly risky journey on their way to the future gonads!

Confinement leads to nuclear rupture and DNA damage in cancer cells – we wondered whether a similar phenomenon might be at play in PGC migration. At later stages, and when we increased confinement, we saw more PGCs rupturing and dying.

We show that the development of tissues around PGCs leads to less space for them to migrate through and increasing stiffness of the environment around them. These changes, along with the development of the basement membrane, lead to PGCs being subject to increasing physical confinement.

They do this by first extending long protrusions through the basement membrane (Kate calls these “snorfls”), which eventually widen before the PGC moves into the next tissue. (magenta = PGC, cyan = nuclei)

Along the way, they are not only surrounded by ECM, but also produce it themselves, providing a possible scaffold for their movement. But the ECM also gets in the way – PGCs must eventually cross a basement membrane to continue their journey. (magenta = PGC, yellow = ECM, green = hindgut endoderm)

We show that PGCs in the mouse migrate with long, dynamic, actin rich protrusions – a strategy different from those used by PGCs in our other favorite model organisms like flies and zebrafish. (green = actin, magenta = PGC)

Kate and I dove into the remarkable and understudied migration of primordial germ cells (PGCs) in the mouse embryo – a multi-day long trek through developing embryonic tissues that we show poses surprising risks to these essential cells. (magenta = PGC, cyan = nuclei)