Over-expression of DMRT1 induces the male pathway in embryonic chicken gonads

Luke S. Lambeth; Christopher S. Raymond; Kelly N. Roeszler; Asato Kuroiwa; Tomohiro Nakata; David Zarkower; Craig A. Smith

doi:10.1016/j.ydbio.2014.02.012

Over-expression of DMRT1 induces the male pathway in embryonic chicken gonads

Luke S. Lambeth, Christopher S. Raymond, Kelly N. Roeszler, Asato Kuroiwa, Tomohiro Nakata, David Zarkower, Craig A. Smith

Genetics, Cell Biology and Development (TMED)

Research output: Contribution to journal › Article › peer-review

94 Scopus citations

Abstract

DMRT1 encodes a conserved transcription factor with an essential role in gonadal function. In the chicken, DMRT1 in located on the Z sex chromosome and is currently the best candidate master regulator of avian gonadal sex differentiation. We previously showed that knockdown of DMRT1 expression during the period of sexual differentiation induces feminisation of male embryonic chicken gonads. This gene is therefore necessary for proper testis development in the chicken. However, whether it is sufficient to induce testicular differentiation has remained unresolved. We show here that over-expression of DMRT1 induces male pathway genes and antagonises the female pathway in embryonic chicken gonads. Ectopic DMRT1 expression in female gonads induces localised SOX9 and AMH expression. It also induces expression of the recently identified Z-linked male factor, Hemogen (HEMGN). Masculinised gonads show evidence of cord-like structures and retarded female-type cortical development. Furthermore, expression of the critical feminising enzyme, aromatase, is reduced in the presence of over-expressed DMRT1. These data indicate that DMRT1 is an essential sex-linked regulator of gonadal differentiation in avians, and that it likely acts via a dosage mechanism established through the lack of global Z dosage compensation in birds.

Original language	English (US)
Pages (from-to)	160-172
Number of pages	13
Journal	Developmental Biology
Volume	389
Issue number	2
DOIs	https://doi.org/10.1016/j.ydbio.2014.02.012
State	Published - May 15 2014

Bibliographical note

Funding Information:
The authors thank Dr. Olivier Serralbo (Australian Regenerative Medicine Institute, Melbourne) for demonstrating the in ovo electroporation technique. LL is supported by the Poultry CRC for Sex Determination . CAS is funded through an Australian Research Council (ARC) Future Fellowship , while KR is funded through an ARC Discovery Project Grant . This research was conducted within the Poultry CRC, established and supported under the Australian Government׳s Cooperative Research Centres Program and the University of Minnesota Medical School , supported by the NIH (Grant GM59152 to DZ) and the Minnesota Medical Foundation . The Murdoch Childrens Research Institute (MCRI) is supported by the Victorian Government׳s Operational Infrastructure Support Program .

Keywords

AMH
DMRT1
Embryonic chicken gonad
HEMGN
SOX9
Sex determination

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title = "Over-expression of DMRT1 induces the male pathway in embryonic chicken gonads",

abstract = "DMRT1 encodes a conserved transcription factor with an essential role in gonadal function. In the chicken, DMRT1 in located on the Z sex chromosome and is currently the best candidate master regulator of avian gonadal sex differentiation. We previously showed that knockdown of DMRT1 expression during the period of sexual differentiation induces feminisation of male embryonic chicken gonads. This gene is therefore necessary for proper testis development in the chicken. However, whether it is sufficient to induce testicular differentiation has remained unresolved. We show here that over-expression of DMRT1 induces male pathway genes and antagonises the female pathway in embryonic chicken gonads. Ectopic DMRT1 expression in female gonads induces localised SOX9 and AMH expression. It also induces expression of the recently identified Z-linked male factor, Hemogen (HEMGN). Masculinised gonads show evidence of cord-like structures and retarded female-type cortical development. Furthermore, expression of the critical feminising enzyme, aromatase, is reduced in the presence of over-expressed DMRT1. These data indicate that DMRT1 is an essential sex-linked regulator of gonadal differentiation in avians, and that it likely acts via a dosage mechanism established through the lack of global Z dosage compensation in birds.",

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author = "Lambeth, {Luke S.} and Raymond, {Christopher S.} and Roeszler, {Kelly N.} and Asato Kuroiwa and Tomohiro Nakata and David Zarkower and Smith, {Craig A.}",

note = "Funding Information: The authors thank Dr. Olivier Serralbo (Australian Regenerative Medicine Institute, Melbourne) for demonstrating the in ovo electroporation technique. LL is supported by the Poultry CRC for Sex Determination . CAS is funded through an Australian Research Council (ARC) Future Fellowship , while KR is funded through an ARC Discovery Project Grant . This research was conducted within the Poultry CRC, established and supported under the Australian Government׳s Cooperative Research Centres Program and the University of Minnesota Medical School , supported by the NIH (Grant GM59152 to DZ) and the Minnesota Medical Foundation . The Murdoch Childrens Research Institute (MCRI) is supported by the Victorian Government׳s Operational Infrastructure Support Program . ",

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AU - Nakata, Tomohiro

AU - Zarkower, David

AU - Smith, Craig A.

N1 - Funding Information: The authors thank Dr. Olivier Serralbo (Australian Regenerative Medicine Institute, Melbourne) for demonstrating the in ovo electroporation technique. LL is supported by the Poultry CRC for Sex Determination . CAS is funded through an Australian Research Council (ARC) Future Fellowship , while KR is funded through an ARC Discovery Project Grant . This research was conducted within the Poultry CRC, established and supported under the Australian Government׳s Cooperative Research Centres Program and the University of Minnesota Medical School , supported by the NIH (Grant GM59152 to DZ) and the Minnesota Medical Foundation . The Murdoch Childrens Research Institute (MCRI) is supported by the Victorian Government׳s Operational Infrastructure Support Program .

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AB - DMRT1 encodes a conserved transcription factor with an essential role in gonadal function. In the chicken, DMRT1 in located on the Z sex chromosome and is currently the best candidate master regulator of avian gonadal sex differentiation. We previously showed that knockdown of DMRT1 expression during the period of sexual differentiation induces feminisation of male embryonic chicken gonads. This gene is therefore necessary for proper testis development in the chicken. However, whether it is sufficient to induce testicular differentiation has remained unresolved. We show here that over-expression of DMRT1 induces male pathway genes and antagonises the female pathway in embryonic chicken gonads. Ectopic DMRT1 expression in female gonads induces localised SOX9 and AMH expression. It also induces expression of the recently identified Z-linked male factor, Hemogen (HEMGN). Masculinised gonads show evidence of cord-like structures and retarded female-type cortical development. Furthermore, expression of the critical feminising enzyme, aromatase, is reduced in the presence of over-expressed DMRT1. These data indicate that DMRT1 is an essential sex-linked regulator of gonadal differentiation in avians, and that it likely acts via a dosage mechanism established through the lack of global Z dosage compensation in birds.

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Over-expression of DMRT1 induces the male pathway in embryonic chicken gonads

Abstract

Bibliographical note

Keywords

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