Molecular Mechanisms of Germ Cell Formation

对生殖细胞分化的深入了解对生殖和发育生物学几乎所有方面都至关重要。为了增加我们的基础知识，我们用小鼠、两栖动物、鱼类和果蝇研究了生殖细胞形成的分子和细胞机制。我们的发现包括：(1)促性腺激素、11-酮-睾酮(11-KT)、11-KT受体、激活素I和II受体以及几种CDK/Cyclin复合体在启动鳗鱼精子发生中的重要作用；(2)罗非鱼卵巢分化对雌激素的依赖；(3)金鱼卵母细胞MPF激活/失活机制的阐明。2.(1)确定WT-1、激活素和IGF-I是FSH诱导的精原细胞分化和启动Newt睾丸减数分裂的介质：(2)催乳素在Newt精原细胞凋亡中的重要作用。3.(1)Nanos和Pumilio蛋白参与调控果蝇发育过程中极细胞向性腺的迁移；(2)新基因indora在果蝇极细胞分化过程中的重要作用。4.(1)鉴定NeuRegin-b/ErbB3是小鼠原始生殖细胞(PGC)发育的关键因子；(2)小鼠上皮细胞在5.5-6.0DPC的培养中自主分化为PGC的能力。5.(1)在果蝇早期胚胎发育过程中，X/A比例在转录水平上调节SXL的表达；(2)斑马鱼DAZ同源基因作为生殖细胞发育的介体。6.(1)小鼠精卵结合的新基因calmegin的本质；(2)鉴定了80多个在小鼠睾丸单倍体生殖细胞中特异表达的克隆

A solid understanding of germ cell differentiation is critical to virtually all aspects of reproductive and developmental biology. To increase our basic knowledge, the molecular and cellular mechanisms of germ cell formation were investigated using mice, amphibians, fishes and Drosophila. Our findings include : 1. (1) The critical importance of gonadotropin, 11-ketotestosterone (11-KT), 11-KT receptors, activin type I and II receptors and several CDK/cyclin complexes to initiating spermatogenesis in Japanese eel ; (2) the dependence of ovarian differentiation on estrogen in tilapia ; (3) elucidation of the MPF activation/inactivation mechanisms in goldfish oocytes. 2. (1) Identification of WT-1, activin and IGF-I as mediators of FSH-induced spermatogonial differentiation and initiation of meiosis in newt testes ; (2) The important role of prolactin in newt spermatogonial apoptosis. 3. (1) The involvement of the Nanos and Pumilio proteins in regulating polar cell migration to the gonads during Drosophila development ; (2) the essential role the novel gene indora plays during differentiation of Drosophila polar cells. 4. (1) Identification of neuregulin-b/ErbB3 as a critical factor for primordial germ cell (PGC) development in mice ; (2) the ability of the mouse epiblast to autonomously differentiate into PGCs in culture between 5.5 and 6.0 dpc. 5. (1) The X/A ratio transcriptionally regulates Sxl expression during early embryogenesis in Drosophila ; (2) characterization of a zebrafish DAZ homologue as a mediator of germ cell development. 6. (1) The essential nature of calmegin, a novel gene, for sperm-egg binding in mouse ; (2) identification of more than 80 clones that are specifically expressed in the haploid germ cells of mouse testes