High-throughput sequencing reshapes chicken sex determination and differentiation: From candidate genes to hierarchical regulatory networks.
- 1Key Laboratory of Animal Genetics, Breeding and Molecular Design of Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou, China.
- 2Poultry Research Institute, Chinese Academy of Agricultural Science/Jiangsu Institute of Poultry Science, Yangzhou, China.
- 3Key Laboratory of Animal Genetics, Breeding and Molecular Design of Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou, China. Electronic address: [email protected].
Abstract
Chicken sex determination and differentiation have long lacked a highly integrated and hierarchically defined framework comparable to the mammalian SRY-SOX9 paradigm. This is partly attributable to avian-specific biological features, including the ZZ/ZW sex chromosome system, incomplete dosage compensation, and cell-autonomous sex identity, as well as the limited resolution of early low-throughput approaches. Here, we systematically review how high-throughput sequencing technologies have transformed the conceptual framework of chicken sex determination and differentiation, from classical morphological and endocrine studies and candidate-gene identification to bulk RNA sequencing, multi-omics, and single-cell and single-nucleus analyses. Current evidence supports a model in which DMRT1/Z-chromosome dosage bias provides the primary male-promoting signal, whereas sex determination and differentiation are executed through a multilayered regulatory network involving the FOXL2-CYP19A1/aromatase-estrogen axis, non-coding RNAs, epigenetic modifications, RNA modifications, and cell-type-specific regulatory programs. These advances have shifted the field from candidate-gene studies and cross-species borrowing toward the establishment of a bird-specific theoretical framework for sex determination. We further highlight key unresolved issues, including insufficient temporal resolution during critical developmental windows, limited causal validation of candidate regulators, and incomplete integration of multi-omics datasets across molecular, cellular, and spatial levels. Future studies integrating high-resolution spatiotemporal profiling, functional perturbation, and comparative avian analyses will be essential for resolving the remaining regulatory hierarchy. Overall, this review provides a comprehensive framework for understanding the molecular basis of chicken sex determination and differentiation and offers a theoretical foundation for future advances in poultry sex-control technologies and precision breeding.
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BibTeX
@article{lv2026highthroughput,
title = {{High-throughput sequencing reshapes chicken sex determination and differentiation: From candidate genes to hierarchical regulatory networks.}},
author = {Xiaoqian Lv and Xu Tan and Qiang Wei and Zeling Yao and Xiaosa Wang and Yingjie Niu and Kai Jin and Bichun Li and Yixiu Jiang and Qisheng Zuo},
journal = {Poultry science},
year = {2026},
month = oct,
doi = {10.1016/j.psj.2026.107889},
url = {https://europepmc.org/article/MED/42887304},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - High-throughput sequencing reshapes chicken sex determination and differentiation: From candidate genes to hierarchical regulatory networks.
AU - Xiaoqian Lv
AU - Xu Tan
AU - Qiang Wei
AU - Zeling Yao
AU - Xiaosa Wang
AU - Yingjie Niu
AU - Kai Jin
AU - Bichun Li
AU - Yixiu Jiang
AU - Qisheng Zuo
PY - 2026
DA - 2026/10/05
JO - Poultry science
DO - 10.1016/j.psj.2026.107889
UR - https://europepmc.org/article/MED/42887304
AB - Chicken sex determination and differentiation have long lacked a highly integrated and hierarchically defined framework comparable to the mammalian SRY-SOX9 paradigm. This is partly attributable to avian-specific biological features, including the ZZ/ZW sex chromosome system, incomplete dosage compensation, and cell-autonomous sex identity, as well as the limited resolution of early low-throughput approaches. Here, we systematically review how high-throughput sequencing technologies have transformed the conceptual framework of chicken sex determination and differentiation, from classical morphological and endocrine studies and candidate-gene identification to bulk RNA sequencing, multi-omics, and single-cell and single-nucleus analyses. Current evidence supports a model in which DMRT1/Z-chromosome dosage bias provides the primary male-promoting signal, whereas sex determination and differentiation are executed through a multilayered regulatory network involving the FOXL2-CYP19A1/aromatase-estrogen axis, non-coding RNAs, epigenetic modifications, RNA modifications, and cell-type-specific regulatory programs. These advances have shifted the field from candidate-gene studies and cross-species borrowing toward the establishment of a bird-specific theoretical framework for sex determination. We further highlight key unresolved issues, including insufficient temporal resolution during critical developmental windows, limited causal validation of candidate regulators, and incomplete integration of multi-omics datasets across molecular, cellular, and spatial levels. Future studies integrating high-resolution spatiotemporal profiling, functional perturbation, and comparative avian analyses will be essential for resolving the remaining regulatory hierarchy. Overall, this review provides a comprehensive framework for understanding the molecular basis of chicken sex determination and differentiation and offers a theoretical foundation for future advances in poultry sex-control technologies and precision breeding.
SN - 0032-5791
SN - 1525-3171
ER -