Mouse primordial germ cells lacking β1 integrins enter the germline but fail to migrate normally to the gonads

TLDR

Primordial germ cells, the progenitors of gametes, are specified during gastrulation, migrate through the hindgut to the developing gonads, yet the molecular mechanisms guiding this migration remain poorly understood. This study investigates whether integrin family receptors are essential for primordial germ cell migration. Using GFP‑labeled mice, the authors isolated PGCs at various stages by flow cytometry and profiled integrin subunit expression with flow, immunocytochemistry, and RT‑PCR. β1‑integrin–deficient PGCs enter the germline but fail to efficiently colonize the gonads, whereas deletion of α3, α6, or αV integrins causes no major migration defects, indicating a specific role for β1‑containing integrins in germline development.

Abstract

Abstract Primordial germ cells are the founder cells of the gametes. They are set aside at the initial stages of gastrulation in mammals, become embedded in the hind-gut endoderm, then actively migrate to the sites of gonad formation. The molecular basis of this migration is poorly understood. Here we sought to determine if members of the integrin family of cell surface receptors are required for primordial germ cell migration, as integrins have been implicated in the migration of several other motile cell types. We have established a line of mice which express green fluorescent protein in germline cells that has enabled us to efficiently purify primordial germ cells at different stages by flow cytometry. We have catalogued the spectrum of integrin subunit expression by primordial germ cells during and after migration, using flow cytometry, immunocytochemistry and RT-PCR. Through analysis of integrin β1−/−→wild-type chimeras, we show that embryonic cells lacking β1 integrins can enter the germline. However, integrin β1−/− primordial germ cells do not colonize the gonad efficiently. Embryos with targeted deletion of integrin subunit α3, α6, or αV show no major defects in primordial germ cell migration. These results demonstrate a role for β1-containing integrins in the development of the germline, although an equivalent role for α integrin subunit(s) has yet to be established.