THE ROLE OF BAX IN APOPTOSIS OF ECTOPIC PRIMORDIAL GERM CELLS IN THE MOUSE
Primordial germ cells (PGCs) are the mothers of all stem cells, capable of giving rise to every other cell in the body. These totipotent cells are set aside early in development via locational cues, and migrate to the genital ridges to form the gonad proper. The migration process for PGCs is not overly efficient, with PGCs migrating aberrantly throughout the migration process. The PGCs that migrate successfully into the gonadal anlagen aggregate with other PGCs, become non-motile, and continue to proliferate within the gonad proper. Ectopic post-migratory PGCs are present in mice near the developing gonads and in the midline mesenchymal tissue and hindgut along the route of PGC migration up until E13.5, when a wave of PGC apoptosis eliminates intragonadal PGCs, and possibly ectopic PGCs as none are found at E14.5 in wild-type embryos. In Bax homozygous mutant mice (Bax -/- ), midline and capsular PGCs are seen as late as E15.5, and ectopic PGCs were observed at E18.5 near the dorsal aorta in the lumbar region of the developing embryo. Germ cell markers that are normally turned off prior to E14.5 in gonadal PGCs are present in E14.5 ectopic PGCs, and begin to decrease expression at ~E15.5. In crude cell cultures, E10.5 Bax -/- PGCs proliferate and have an increased short-term survival when compared to wild-type PGCs from littermates, however Bax -/- PGCs do eventually die. Addition of ACK2, a c-kit blocking antibody, to the cell cultures partially reduced survival of Bax -/- PGCs, however the majority of PGCs survive. I propose that removal of migratory and early post-migratory ectopic germ cells proceeds through a Bax-dependent pathway, whereas removal of ectopic PGCs beginning at E15.5 operates through a Bax-independent mechanism. In addition, the loss of the Steel/c-kit cell signaling survival pathway promotes apoptosis at least partially through a Bax-dependent mechanism during PGC migration. The removal of E13.5 ectopic PGCs is Bax-dependent, and it is possible that an intragonadal apoptotic wave observed at E13.5 may also be Bax-dependent.
School:University of Cincinnati
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:primordial germ cells bax c kit apoptosis ectopic
Date of Publication:01/01/2003