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.
authors.affiliation: Murdoch Childrens Research Institute, Royal Children׳s Hospital, Flemington Road, Parkville, Melbourne, Victoria 3052, Australia; Poultry Cooperative Research Centre, Armidale, NSW, Australia.
authors.forename: Luke S
authors.initials: LS
authors.lastname: Lambeth
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis 55455, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Raymond
authors.affiliation: Murdoch Childrens Research Institute, Royal Children׳s Hospital, Flemington Road, Parkville, Melbourne, Victoria 3052, Australia.
authors.forename: Kelly N
authors.initials: KN
authors.lastname: Roeszler
authors.affiliation: Laboratory of Animal Cytogenetics, Department of Biological Sciences, Faculty of Science, Hokkaido University, Hokkaido 060-0810, Japan.
authors.forename: Asato
authors.initials: A
authors.lastname: Kuroiwa
authors.affiliation: Graduate School of Life Science, Hokkaido University, Hokkaido 060-0810, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakata
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis 55455, USA.
authors.forename: David
authors.initials: D
authors.lastname: Zarkower
authors.affiliation: Murdoch Childrens Research Institute, Royal Children׳s Hospital, Flemington Road, Parkville, Melbourne, Victoria 3052, Australia; Poultry Cooperative Research Centre, Armidale, NSW, Australia; Department of Paediatrics, The University of Melbourne, Victoria, Australia; Department of Zoology, The University of Melbourne, Victoria, Australia. Electronic address: craig.smith@mcri.edu.au.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Smith
mesh_terms: D000818:Animals; D054304:Anti-Mullerian Hormone / Q000378:metabolism; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D002642:Chick Embryo; D018274:Electroporation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006066:Gonads / Q000196:embryology* / Q000378:metabolism*; D008297:Male; D055758:SOX9 Transcription Factor / Q000378:metabolism; D019849:Sex Determination Processes; D013737:Testis / Q000196:embryology / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C110547:DMRT1 protein; D055758:SOX9 Transcription Factor; D014157:Transcription Factors; D054304:Anti-Mullerian Hormone; D001141:Aromatase
keywords: AMH; DMRT1; Embryonic chicken gonad; HEMGN; SOX9; Sex determination