期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2020909118
关键词
chicken embryo; gonadal development; testis differentiation; ovary differentiation; sex determination
资金
- Biotechnology and Biological Sciences Research Council [BB/N018672/1]
- Roslin Institute (RI) Institute Strategic Programme [BB/P0.13732/1, BB/P013759/1]
- Francis Crick Institute
- Cancer Research UK [FC001107]
- UK Medical Research Council [FC001107, U117512772]
- Wellcome Trust [FC001107]
- BBSRC [BBS/E/D/30002276, BB/N018672/1, BB/N018680/1] Funding Source: UKRI
- MRC [MC_U117562207] Funding Source: UKRI
In birds, sex determination is thought to depend on a sex chromosome gene dosage mechanism, with the gene DMRT1 playing a key role. Experiments showed that ZZ chickens lacking DMRT1 developed ovaries instead of testes, while blocking estrogen synthesis in ZW embryos led to testis development, highlighting the interconnected roles of DMRT1 and estrogen in avian sex determination.
In birds, males are the homogametic sex (ZZ) and females the heterogametic sex (ZW). Primary sex determination is thought to depend on a sex chromosome gene dosage mechanism, and the most likely sex determinant is the Z chromosome gene Doublesex and Mab-3-Related Transcription factor 1 (DMRT1). To clarify this issue, we used a CRISPR-Cas9-based monoallelic targeting approach and sterile surrogate hosts to generate birds with targeted mutations in the DMRT1 gene. The resulting chromosomally male (ZZ) chicken with a single functional copy of DMRT1 developed ovaries in place of testes, demonstrating the avian sex-determining mechanism is based on DMRT1 dosage. These ZZ ovaries expressed typical female markers and showed clear evidence of follicular development. However, these ZZ adult birds with an ovary in place of testes were indistinguishable in appearance to wild-type adult males, supporting the concept of cell-autonomous sex identity (CASI) in birds. In experiments where estrogen synthesis was blocked in control ZW embryos, the resulting gonads developed as testes. In contrast, if estrogen synthesis was blocked in ZW embryos that lacked DMRT1, the gonads invariably adopted an ovarian fate. Our analysis shows that DMRT1 is the key sex determination switch in birds and that it is essential for testis development, but that production of estrogen is also a key factor in primary sex determination in chickens, and that this production is linked to DMRT1 expression.
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