遗传 ›› 2024, Vol. 46 ›› Issue (9): 677-689.doi: 10.16288/j.yczz.24-146
收稿日期:
2024-05-23
修回日期:
2024-07-04
出版日期:
2024-09-20
发布日期:
2024-08-01
通讯作者:
何祖勇,博士,副教授,研究方向:动物遗传与育种。E-mail: zuyonghe@foxmail.com作者简介:
杨敏,硕士研究生,专业方向:生物与医药。E-mail: yangmin32@163.com
基金资助:
Min Yang(), Siyuan Lin, Changqi Yang, Yaosheng Chen, Zuyong He(
)
Received:
2024-05-23
Revised:
2024-07-04
Published:
2024-09-20
Online:
2024-08-01
Supported by:
摘要:
性别决定指的是胚胎发育早期,在转录因子的精确调控下,具有双重分化潜能的性腺向睾丸(雄性)或卵巢(雌性)方向转变的过程。SOX9(SRY-box transcription factor 9)是哺乳动物发育过程中的多功能转录因子,在性别决定及随后的雄性生殖器官发育中发挥关键作用。近年来相关研究表明,SOX9上游的多个增强子也在性别决定过程中扮演着重要的角色。本文主要对SOX9及其与性腺发育相关的增强子在性别决定中的研究进展进行了综述,以期加深人们对SOX9在性别决定中调控作用机制的认识,为加快动物性别控制技术研究提供理论参考。
杨敏, 林思远, 杨长淇, 陈瑶生, 何祖勇. SOX9及其增强子在哺乳动物性别决定中的研究进展[J]. 遗传, 2024, 46(9): 677-689.
Min Yang, Siyuan Lin, Changqi Yang, Yaosheng Chen, Zuyong He. Progress on SOX9 and its enhancers in mammalian sex determination[J]. Hereditas(Beijing), 2024, 46(9): 677-689.
图2
哺乳动物性别决定过程中的调控模式 在XY个体中,Sry在多个正向调节因子的调控下,在未分化性腺的体细胞中开始表达,诱导未分化性腺向雄性性腺(睾丸)方向分化。Sry表达后激活Sox9表达,Sox9则与Fgf9、Fgfr2、Pgd2等互相激活,形成一个正反馈循环。Sox9表达的启动和维持会触发睾丸分化所需的几个基因的表达,包括 Amh、Ptgds和Dhh等,同时抑制雌性性别决定通路基因的表达,促进未分化性腺发育为睾丸。在XX个体中,卵巢分化最初由 Wnt4和Rspo1主导,它们负责上调和稳定β-catenin。在性别决定发生后,激活的Wnt4/Rspo1/β-catenin信号通路抑制了Sox9和Fgf9的表达,使支持类体细胞前体向卵巢颗粒细胞分化。Wnt4和Rspo1表达的同时,Foxl2在双潜能性腺的支持类体细胞中也开始表达,在这些雌性性别决定通路相关因子的作用下,未分化的性腺最终发育为卵巢。"
图3
人类SOX9上游基因组视图 SOX9基因位于人类17号染色体上,其邻近基因位于上游2 Mb。SOX9上游两个区域与性逆转有关:一个是 XXSR(浅粉色),是一个24 kb的区域,位于SOX9上游559~583 kb处,其重复导致女性性别逆转;第二个称为XYSR(浅蓝色),是一个32.5 kb的区域,位于SOX9更上游607~639 kb处,其缺失导致男性性别逆转。在46, XX性反转男性综合征患者中发现的迄今为止SOX9 的最小致病性DNA重复片段[70]是位于XYSR区域。在人类XXSR与XYSR区域内,分别鉴定了eSR-A、eSR-B两个关键性腺增强子;除XXSR与XYSR区域外,也鉴定到其他SOX9上游增强子,如eALDI和TES。"
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