性别是生物界最普遍的特征之一。生物界的性别决定系统虽然千差万别，但相关基因的功能往往是保守的。阐明性别决定和分化的调控机制是发育生物学研究中重要的科学问题，对于促进人口生殖健康也有着积极的借鉴意义。目前，性别决定的一些重要基因已被鉴定出来，分子调控机制得到初步揭示。但现有研究往往只局限于少数基因，对基因调控网络的全景图像难以形成整体认识。本项目以青鳉鱼为模式生物，利用系统生物学策略，包括高通量测量和系统干扰实验，研究控制性别决定的基因调控网络。青鳉的性别决定系统明确，又有性别连锁的色素基因，使我们能够分别追踪雌雄性腺在性别决定阶段的转录组变化，从而全面掌握性别决定的分子基础并鉴定出新的调控基因；再通过系统的干扰实验，解析基因之间的调控关系，构建出相应的基因调控网络。本项目的完成将使我们较系统地理解青鳉性别决定过程中的分子基础及调控机制，为人类生殖健康研究提供重要信息。

Sex dimorphism is one of the most pervasive features of organisms. The sex determination systems are considerably diverse, but the functions of related genes are likely conserved. Elucidating the regulatory mechanisms governing sex determination and sex differentiation is not only a scientific challenge, but also of great medical interest. To date, several critical genes have been identified, and properties of the regulatory mechanisms are emerging. However, current studies often focus on a few genes, which provide limited views of the global regulatory logic. We seek to study the sex determination process, using medaka as the model organism and using a systems biology strategy that includes high-throughput measurements and systematic perturbation experiments. Medaka has a clear genetic sex determination system. In addition, a special transgenic line carrying an early-expressed sex-linked pigment marker is available. These features enable us to track the transcriptomic changes of gonads in a sex-specific manner during the sex determination process. Thus, we can identify all related genes with their dynamic expression profiles, and systematically understand the molecular basis. Furthermore, using perturbation experiments, we can dissolve the regulatory logic among genes, and construct the gene regulatory network underlying this developmental process. The accomplishment of this project will provide us a global landscape of the molecular basis, improve our understanding of the regulatory mechanisms directing the sex determination in medaka, and be informative for medical research regarding human reproductive science.