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

• Published in: Developmental biology Vol. 389; no. 2; pp. 160 - 172
• Main Authors: Lambeth, Luke S., Raymond, Christopher S., Roeszler, Kelly N., Kuroiwa, Asato, Nakata, Tomohiro, Zarkower, David, Smith, Craig A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.05.2014
• Subjects: AMH; Animals; Anti-Mullerian Hormone - metabolism; Aromatase - genetics; Aromatase - metabolism; Chick Embryo; DMRT1; Electroporation; Embryonic chicken gonad; Female; Gene Expression Regulation, Developmental; Gonads - embryology; Gonads - metabolism; HEMGN; Male; Sex determination; Sex Determination Processes; SOX9; SOX9 Transcription Factor - metabolism; Testis - embryology; Testis - metabolism; Time Factors; Transcription Factors - metabolism; HEMGN; DMRT1; Sex determination; Embryonic chicken gonad; FOXL2; SOX9; AMH; PFA/PBS; PCR; RCASBP/A
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2014.02.012

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. •DMRT1 is male up-regulated in embryonic chicken gonads before HEMGN, SOX9 and AMH.•Over-expression of DMRT1 in female gonads induces HEMGN, SOX9 and AMH expression.•Expression of Aromatase protein is retarded in female gonads over-expressing DMRT1.•DMRT1 can activate the male pathway and antagonise the female pathway in chicken.