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Mechanisms of Mouse Primordial Germ Cell Migration: The Role of SDF-1 and Cytoskeletal Dynamics https://doi.org/10.17863/CAM.128916 Foster, William Paluch, Ewa Primordial germ cells (PGCs) are the earliest embryonic precursors to the gametes: spermatozoa and oocytes. In many species, PGCs must migrate to the embryonic gonad during early development in order to produce functional gametes. Failure to reach the gonad increases the risk of tumorigenesis, leading to extragonadal germ cell tumours. In spite of their importance, the mechanisms and regulation of mammalian PGC migration are poorly understood. In this work, we used PGC-like cells (PGCLCs), which are embryonic stem cell-derived analogues of migratory-stage PGCs, to investigate the modes of migration employed by mouse PGCs. To mimic the three-dimensional confinement encountered by PGCs migrating in vivo, we used flat confinement devices where cells move freely in a plane but are confined vertically. We found that PGCLCs combined different migration modes in confined environments. Specifically, PGCLCs displayed switches between amoeboid (bleb-based) and mesenchymal (actin protrusion-driven) modes of migration. Interestingly, both mesenchymal and amoeboid phases could be associated with persistent cell trajectories. We examined the role of stromal cell-derived factor-1 (SDF-1) in regulating PGCLC behaviour. We examined the role of stromal cell-derived factor-1 (SDF-1) in regulating PGCLC behaviour. SDF-1 is expressed along the migratory route of PGCs in vivo, and has previously been proposed to have a role in the migration and/or survival of PGCs. We found that SDF-1 minimally affects PGCLC survival and has no significant effect on proliferation. However, SDF-1 does exert a pro-migratory effect, enhancing speed and persistence, and functions as a positive chemotactic agent for PGCLCs. Together, our data suggest that PGCs can migrate through amoeboid or mesenchymal modes, and that SDF-1 has pro-migratory and chemotactic functions. These findings offer valuable insight into a relatively elusive aspect of mammalian development, and pave the way towards a greater understanding of pathological mismigration of PGCs. University of Cambridge 2025-09-30 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/400935 embargo 2027-04-01 https://www.repository.cam.ac.uk/bitstreams/1315aae1-9620-457b-afe8-7f648bf97354/download e7b4269eb8566730f91d452b5fa1fd48 https://www.repository.cam.ac.uk/bitstreams/e8c2d8f7-4f94-4dc2-be5b-8412d1a933d3/download 87eda9de84448d1f82354d60eee3eb5f http://purl.org/NET/rdflicense/allrightsreserved cell migration primordial germ cell