Primary sex determination in birds depends on DMRT1 dosage, but gonadal sex does not determine adult secondary sex characteristics.
chicken embryo
gonadal development
ovary differentiation
sex determination
testis differentiation
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
09 03 2021
09 03 2021
Historique:
entrez:
4
3
2021
pubmed:
5
3
2021
medline:
17
8
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33658372
pii: 2020909118
doi: 10.1073/pnas.2020909118
pmc: PMC7958228
pii:
doi:
Substances chimiques
Avian Proteins
0
DMRT1 protein
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust
ID : FC001107
Pays : United Kingdom
Organisme : Worldwide Cancer Research
ID : 13-1270
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/N018672/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U117562207
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001107
Pays : United Kingdom
Organisme : Medical Research Council
ID : U117512772
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC001107
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/D/20320000
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2021 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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