Dazl deficiency leads to embryonic arrest of germ cell development in XY C57BL/6 mice.
Genes of the DAZ family play critical roles in germ cell development in mammals and other animals. In mice, Dazl mRNA is first observed at embryonic day 11.5 (E11.5), but previous studies using Dazl-deficient mice of mixed genetic background have largely emphasized postnatal spermatogenic defects. Using an inbred C57BL/6 background, we show 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 MVH protein) was reduced in XY Dazl-/- gonads. By E15.5, most remaining germ cells in XY Dazl-/- embryos exhibited apoptotic morphology, and XY Dazl-/- gonads contained increased numbers of TUNEL-positive cells. The rare XY Dazl-/- germ cells that persisted until birth maintained a nuclear morphology that resembled that of wildtype germ cells at E12.5-E13.5, a critical developmental period when XY germ cells lose pluripotency and commit to a spermatogonial fate. We propose that Dazl is required as early 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.
Lin
Yanfeng
Y
Howard Hughes Medical Institute, Whitehead Institute, 9 Cambridge Center, Cambridge, MA 02142, USA.
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David C
DC
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D047108:Embryonic Development; D005260:Female; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism*; D006066:Gonads / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D015415:Biomarkers; C508515:DAZL protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins