Sex reversal and comparative data undermine the W chromosome and support Z-linked DMRT1 as the regulator of gonadal sex differentiation in birds

Claire E. Hirst, Andrew T. Major, Katie L. Ayers, Rosie J. Brown, Mylene Mariette, Timothy B. Sackton, Craig A. Smith

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Abstract

The exact genetic mechanism regulating avian gonadal sex differentiation has not been completely resolved. The most likely scenario involves a dosage mechanism, whereby the Z-linked DMRT1 gene triggers testis development. However, the possibility still exists that the female-specific W chromosome may harbor an ovarian determining factor. In this study, we provide evidence that the universal gene regulating gonadal sex differentiation in birds is Z-linked DMRT1 and not a W-linked (ovarian) factor. Three candidate W-linked ovarian determinants are HINTW, female-expressed transcript 1 (FET1), and female-associated factor (FAF). To test the association of these genes with ovarian differentiation in the chicken, we examined their expression following experimentally induced female-to-male sex reversal using the aromatase inhibitor fadrozole (FAD). Administration of FAD on day 3 of embryogenesis induced a significant loss of aromatase enzyme activity in female gonads and masculinization. However, expression levels of HINTW, FAF, and FET1 were unaltered after experimental masculinization. Furthermore, comparative analysis showed that FAF and FET1 expression could not be detected in zebra finch gonads. Additionally, an antibody raised against the predicted HINTW protein failed to detect it endogenously. These data do not support a universal role for these genes or for the Wsex chromosome in ovarian development in birds. We found that DMRT1 (but not the recently identified Z-linked HEMGN gene) is male upregulated in embryonic zebra finch and emu gonads, as in the chicken. As chicken, zebra finch, and emu exemplify the major evolutionary clades of birds, we propose that Z-linked DMRT1, and not the W sex chromosome, regulates gonadal sex differentiation in birds.

Original languageEnglish
Pages (from-to)2970-2987
Number of pages18
JournalEndocrinology
Volume158
Issue number9
DOIs
Publication statusPublished - 1 Sep 2017

Cite this

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title = "Sex reversal and comparative data undermine the W chromosome and support Z-linked DMRT1 as the regulator of gonadal sex differentiation in birds",
abstract = "The exact genetic mechanism regulating avian gonadal sex differentiation has not been completely resolved. The most likely scenario involves a dosage mechanism, whereby the Z-linked DMRT1 gene triggers testis development. However, the possibility still exists that the female-specific W chromosome may harbor an ovarian determining factor. In this study, we provide evidence that the universal gene regulating gonadal sex differentiation in birds is Z-linked DMRT1 and not a W-linked (ovarian) factor. Three candidate W-linked ovarian determinants are HINTW, female-expressed transcript 1 (FET1), and female-associated factor (FAF). To test the association of these genes with ovarian differentiation in the chicken, we examined their expression following experimentally induced female-to-male sex reversal using the aromatase inhibitor fadrozole (FAD). Administration of FAD on day 3 of embryogenesis induced a significant loss of aromatase enzyme activity in female gonads and masculinization. However, expression levels of HINTW, FAF, and FET1 were unaltered after experimental masculinization. Furthermore, comparative analysis showed that FAF and FET1 expression could not be detected in zebra finch gonads. Additionally, an antibody raised against the predicted HINTW protein failed to detect it endogenously. These data do not support a universal role for these genes or for the Wsex chromosome in ovarian development in birds. We found that DMRT1 (but not the recently identified Z-linked HEMGN gene) is male upregulated in embryonic zebra finch and emu gonads, as in the chicken. As chicken, zebra finch, and emu exemplify the major evolutionary clades of birds, we propose that Z-linked DMRT1, and not the W sex chromosome, regulates gonadal sex differentiation in birds.",
author = "Hirst, {Claire E.} and Major, {Andrew T.} and Ayers, {Katie L.} and Brown, {Rosie J.} and Mylene Mariette and Sackton, {Timothy B.} and Smith, {Craig A.}",
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Sex reversal and comparative data undermine the W chromosome and support Z-linked DMRT1 as the regulator of gonadal sex differentiation in birds. / Hirst, Claire E.; Major, Andrew T.; Ayers, Katie L.; Brown, Rosie J.; Mariette, Mylene; Sackton, Timothy B.; Smith, Craig A.

In: Endocrinology, Vol. 158, No. 9, 01.09.2017, p. 2970-2987.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Sex reversal and comparative data undermine the W chromosome and support Z-linked DMRT1 as the regulator of gonadal sex differentiation in birds

AU - Hirst, Claire E.

AU - Major, Andrew T.

AU - Ayers, Katie L.

AU - Brown, Rosie J.

AU - Mariette, Mylene

AU - Sackton, Timothy B.

AU - Smith, Craig A.

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