Igf3调控罗非鱼配子发生的分子机制

配子发生是由原始生殖细胞经有丝分裂、减数分裂向成熟配子即精子和卵子分化的复杂过程。胰岛素样生长因子Igf在脊椎动物配子发生具有重要作用。本实验室前期克隆了一个鱼类特有的igf3，它仅在性腺表达，采用CRISPR/Cas9在罗非鱼敲除igf3，发现配子发生受阻，停留在精/卵原细胞阶段，暗示Igf3与鱼类配子发生相关。本项目以罗非鱼为实验对象，研究1）Igf3缺失和过表达对配子发生的影响；2）Igf3缺失和过表达对类固醇发生的影响；3）Igf3对脑-垂体-性腺轴的调控；4）介导Igf3调控配子发生的下游信号通路；5）Igf3受体及内分泌或旁分泌作用模式研究。从缺失功能和获得功能深入分析该生长因子在配子发生中的功能及分子机制、Igf3结合的受体、激活的下游信号通路及作用模式。该研究有助于阐明鱼类特有Igf3存在的生物学意义，为养殖鱼类的生殖调控提供理论依据，在应用上有助于鱼类的繁殖控制。

Gametogenesis is a biological process by which diploid or haploid precursor cells undergo cell division and differentiation to form mature haploid gametes, sperm or egg. Insulin-like growth factors (Igfs) play an important role in vertebrate gametogenesis. Previously, a fish-specific igf3, which was exclusively expressed in the gonads, was successfully cloned by our laboratory. Using CRISPR/Cas9, Igf3 deficiency in tilapia resulted in disruption of gametogenesis, with most germ cell stay with spermatogonia/oogonia stage, indicating that Igf3 was involved in gametogenesis. The main contents of this project are as follows: 1) the effects of Igf3 deletion on male and female gametogenesis; 2) the effects of Igf3 deletion on steroid hormone synthesis; 3) regulation of brain-pituitary-gonad aix by Igf3; 4) the downstream signaling pathways that mediate Igf3 function; 5) identification of Igf3 receptor and its endocrine or paracrine model. The functions, receptor, signal pathway and mechanisms of this growth factor in fish gametogenesis will be comprehensively investigated based on the knockout and transgenic animal models. This study is helpful to elucidate the biological significance of Igf3, which will provides a theoretical basis for the reproductive regulation of cultured fish and contributes to the breeding control of fish.