Primary sex determination in birds depends on DMRT1 dosage, but gonadal sex does not determine adult secondary sex characteristics

Jason Ioannidis, Gunes Taylor, Debiao Zhao, Long Liu, Alewo Idoko-Akoh, Daoqing Gong, Robin Lovell-Badge, Silvana Guioli, Mike McGrew, Mike Clinton

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 DMRT1 (Doublesex and Mab-3 Related Transcription factor 1). To clarify this issue, we used a CRISPR- Cas9 based mono-allelic 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 oestrogen synthesis was blocked in control ZW embryos, the resulting gonads developed as testes. In contrast, if oestrogen synthesis was blocked in ZW embryos 36 that lacked DMRT1, the gonads invariably adopted an ovarian fate. Our analysis shows that 37 DMRT1 is the key sex determination switch in birds and that it is essential for testis development, but that production of oestrogen is also a key factor in primary sex determination in chickens, and that this production is linked to DMRT1 expression.
Original languageEnglish
JournalProceedings of the National Academy of Sciences (PNAS)
Publication statusPublished - 9 Mar 2021

Keywords / Materials (for Non-textual outputs)

  • chicken embryo
  • gonadal development
  • testis differentiation
  • ovary differentiation
  • sex determination,
  • chicken
  • avian
  • oestrogen
  • testis
  • ovary
  • sex chromosomes


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