ArticleProceedings of the National Academy of Sciences of the United States of America2021
Primary sex determination in birds depends on DMRT1 dosage, but gonadal sex does not determine adult secondary sex characteristics.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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91 citing papers in PubMed, 195 citations in OpenAlex.
- Screening and identification of genes for cell autonomous sex identity in chicken somatic cells.Poultry science · 2026Article
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- Transgenerational Epigenetic Effect of Cryopreservation of F0 Rooster Sperm (Animals : an open access journal from MDPI · 2026Article
- Germline organoids develop in vitro from embryonic Taeniopygia guttata (zebra finch) cultures.Scientific reports · 2026Article
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- Deep evolutionary conservation of a sex-determining locus without sequence homology.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Integrated Analysis of Testicular Histology, Sperm Quality, and Gene Expression (Animals : an open access journal from MDPI · 2026Article
- Navigating the Semantic Labyrinth of "Sex" in the Study of Reproductive Trait Evolution.Integrative and comparative biology · 2026Article
- CRISPR/Cas9-mediated TOP1 knockout in chicken DF-1 cells reveals its critical role in apoptosis regulation and genomic stability.Journal of animal science · 2026Article
- Manipulating primordial germ cells from chicken and other bird species.The Journal of reproduction and development · 2026Review
- Sex-specific functional evolution of Dmrt1 in African clawed frogs (Xenopus), and the importance of genetic tipping points in developmental biology.PLoS genetics · 2026Article
- Molecular Tools for Non-invasive Sexing of Wildlife.Advances in experimental medicine and biology · 2026Review
- Cross-Species Validation of Pigeon-Specific CHD1 Primers for Molecular Sexing in Pet Birds.International journal of molecular sciences · 2025Article
- Interleukin 10 controls the balance between tolerance, pathogen elimination, and immunopathology in birds.eLife · 2025Article
- Identification of Key Differentially Expressed Genes During Early Sex Determination in Chicken Embryos.International journal of molecular sciences · 2025Article
- Genome Editing in the Chicken: From PGC-Mediated Germline Transmission to Advanced Applications.International journal of molecular sciences · 2025Review
- Differentiation ofBiomolecules · 2025Article
- DMRT1 haploinsufficiency leads to secondary infertility in XY male rabbits†.Biology of reproduction · 2025Article
31 more citing papers are in PubMed but not listed here.
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10 authors at 3 institutions in 2 countries.
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Abstract
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 Doublesex and Mab-3-Related Transcription factor 1 (DMRT1). To clarify this issue, we used a CRISPR-Cas9-based monoallelic 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 estrogen synthesis was blocked in control ZW embryos, the resulting gonads developed as testes. In contrast, if estrogen synthesis was blocked in ZW embryos that lacked DMRT1, the gonads invariably adopted an ovarian fate. Our analysis shows that DMRT1 is the key sex determination switch in birds and that it is essential for testis development, but that production of estrogen is also a key factor in primary sex determination in chickens, and that this production is linked to DMRT1 expression.
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