哺乳动物配子形成经历从原始生殖细胞形成到配子成熟等多个环节。任何环节都离不开相伴而生的性腺体细胞的发育和分化。申请人的研究工作针对性腺体细胞的分化调控，围绕肿瘤抑制基因Wt1，并结合临床疾病开展，研究成果包括：1，证明原始生殖细胞定向迁移不受生殖嵴体细胞调控；2，发现性腺体细胞谱系特化和维持的新机制，提出了假两性畸形可能的致病机理；3，提出调控睾丸支持细胞极性维持的新机理，发现Wt1基因突变可能导致人类非梗阻性无精子症；4，阐释了调控卵巢颗粒细胞分化的新机制。研究成果丰富和完善了配子发生过程中体细胞分化的调控机制，填补了领域内重要的理论空白，并为相关生殖疾病的临床诊断和治疗提供了新思路。相关研究结果发表在PNAS、PLoS Genet、Hum Mol Genet和BMC Biol等国际期刊，申请人获得人口和计划生育委员会优秀科技成果奖二等奖。

The defect of gamatogenesis is one of the major reasons causing reproductive diseases. Gamatogenesis in mammals is a complex process, including primordial germ cell (PGC) specification, directional migration, meiosis, and maturation of gamates. Dysregulation of any stages during germ cell development will result in aberrant gamatogenesis and reproductive defect in humans. The differentiation of gonadal somatic cells plays critical roles in germ cell development. In the past 5 years, my research work is focusing on the regulation of somatic cell differentiation during gonad development using gene knockout mouse models. The major achievements are listed as following: 1. We demonstrated for the first time that the early stage of PGC migration was not regulated by somatic cells from urigenital ridge, but the precise position of germ cells in genital ridge was dependent on genital ridge somatic cells; 2. We found new mechanisms in lineage specification and maintenance of supporting cells, and the defect of differentiation between steroidogenic and supporting cells is a potential etiology of hermaphroditism. 3. We found new regulatory mechanism for polarity establishment and maintenance of Sertoli cells, and mutation of Wt1 gene is one of etiological causes of non-obstructive azoospermia (NOA) in humans; 4. We found that Wt1 gene was involved in ovarian follicle development by regulating granulosa cell differentiation and mutation of Wt1 was probably one of etiological causes of premature ovarian failure (POF) in humans. The results of our studies provide the new regulatory mechanisms for germ cell development and new etiology causes of germ cell development related reproductive diseases in humans. These results have been published in peer-reviewed journals including PNAS, PLoS Genet, Hum Mol Genet, and BMC Biol et al.