A Role for Dazl in Commitment to Gametogenic Fate in Embryonic Germ Cells of C57BL/6 Mice

Genes of the DAZ family play critical roles in germ cell development in mammalsand other animals. In mice, Dazl mRNA is first observed at embryonic day 11.5 (El 1.5),but previous studies using Dazl-deficient mice of mixed genetic background have largelyemphasized postnatal spermatogenic defects. Using an inbred C57BL/6 background, weshow that Dazl is required for embryonic development and survival of XY germ cells.By E14.5, expression of germ cell markers (Mvh, Oct4, Dppa3/Stella, GCNA and MVHprotein) was reduced in XY Dazl -/gonads. By E15.5, most remaining germ cells in XYDazl -/embryos exhibited apoptotic morphology, and XY Dazl -/gonads containedincreased numbers of TUNEL-positive cells. The rare XY Dazl -/germ cells thatpersisted until birth maintained a nuclear morphology that resembled that of wildtypegerm cells at E12.5-E13.5, a critical developmental period when XY germ cells losepluripotency and commit to a spermatogonial fate. We propose that Dazl is required asearly as E12.5-E13.5, shortly after its expression is first detected, and that inbred Dazl -/-mice of C57BL/6 background provide a reproducible standard for exploring Dazl's roles in embryonic germ cell development.