Capel B
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Annu Rev Physiol. 1998;60:497-523. doi: 10.1146/annurev.physiol.60.1.497.
In mammals the male sex determination switch is controlled by a single gene on the Y chromosome, SRY. SRY encodes a protein with an HMG-like DNA-binding domain, which probably acts as a local organizer of chromatin structure. It is believed to regulate downstream genes in the sex determination cascade, although no direct targets of SRY are clearly known. More genes in the pathway have been isolated through mutation approaches in mouse and human. At least three genes, SRY itself, SOX9, and DAX1, are dosage sensitive, providing molecular evidence that the sex determination step operates at a critical threshold. SRY initiates development of a testis from the bipotential cells of the early gonad. The dimorphic male and female pathways present a rare opportunity to link a pivotal gene in development with morphogenetic mechanisms that operate to pattern an organ and the differentiation of its cells. Mechanisms of testis organogenesis triggered downstream of SRY include pathways of cell signaling controlling cell reorganization, cell proliferation, cell migration, and vascularization.
在哺乳动物中，雄性性别决定开关由Y染色体上的一个单一基因——SRY控制。SRY编码一种具有HMG样DNA结合结构域的蛋白质，该结构域可能作为染色质结构的局部组织者。尽管SRY的直接靶点尚不清楚，但人们认为它在性别决定级联反应中调节下游基因。通过对小鼠和人类的突变研究，已分离出该途径中的更多基因。至少有三个基因，即SRY本身、SOX9和DAX1，对剂量敏感，这为性别决定步骤在临界阈值下起作用提供了分子证据。SRY启动早期性腺双潜能细胞发育为睾丸。两性不同的雄性和雌性发育途径提供了一个难得的机会，将发育中的关键基因与器官形成和细胞分化的形态发生机制联系起来。SRY下游触发的睾丸器官发生机制包括控制细胞重组、细胞增殖、细胞迁移和血管生成的细胞信号通路。
