Maternal control of germline development

摘要 原始生殖细胞(PGC)是配子的前体。PGC开发缺陷导致 生殖细胞减少或消除，并最终导致人类不育，影响10%-15% 情侣。在发育过程中，生殖细胞的出生比性腺的形成早得多。PGC必须 设法在非保护性的躯体环境中长期生存，然后迁徙很长时间 找到性腺的距离。PGC的规范和早期阶段的增殖是至关重要的 以确保足够数量的生殖细胞能够到达性腺并分化为配子。大号 大量文献表明，在迁移到性腺之前，PGC的发育严重依赖于 关于翻译和翻译后的监管机制。了解PGC的发展情况 因此，在翻译和翻译后层面上进行操作与人类生殖高度相关 健康。我的实验室使用非洲爪哇作为模型来研究早期PGC的发展。我们最近报道了 母体死亡末端1(DND1)在卵母细胞中的mRNA不对称定位中起重要作用。之后 受精，Dnd1招募翻译机器到Nanos mRNA并促进Nanos翻译。 通过这种机制，DND1阻止了原生殖细胞的体细胞分化，保护了它们的全能性。 我们最近的初步结果显示，DND1在卵母细胞中被泛素-1迅速降解。 独立的蛋白酶体系统。为了让DND1在之后积累和促进Nanos翻译 受精，编码蛋白酶体激活物的rna必须从dnd1和其他生殖系中分离出来。 卵母细胞向胚胎转变过程中的特定母体因素。我们打算研究这部小说是如何 MRNA易位事件为受精后PGC的启动发育做准备并进行调查 编码蛋白酶体激活子的RNA如何从dnd1和其他生殖系特异的母本中分离出来 卵母细胞向胚胎转化过程中的因素。此外，我们有一个令人兴奋的发现，第一个 PGC增殖波受母体Dzip1调控。我们将确定Dzip1是否监管PGC 通过结合和修饰生殖系特定的RNA结合蛋白的活性进行增殖。 此外，我们将确定作用于Dzip1下游的合子转录网络来控制 PGC增殖。这些工作将对我们理解基本细胞做出重要贡献， 生殖生物学和发育生物学。

Abstract Primordial germ cells (PGCs) are the precursors of the gametes. Defective PGC development results in reduction or elimination of germ cells and ultimately causes infertility in humans, which affects 10–15% of couples. During development, PGCs are born much earlier than the formation of the gonads. PGCs must manage to survive in the non-protective somatic environment for a long time and later migrate long distances to find the gonads. Specification of PGCs and their proliferation during early stages are crucial to ensure that sufficient number of PGCs can reach the gonads and differentiate into gametes. A large body of literature has demonstrated that before migrating into the gonads, PGC development relies heavily on translational and post-translational regulatory mechanisms. Understanding how PGC development is operated at the translational and post-translation levels thus is highly relevant to human reproductive health. My laboratory studies early PGC development using Xenopus as a model. We recently reported that maternal Dead End1 (Dnd1) is important for asymmetric localization of mRNA in the oocyte. After fertilization, Dnd1 recruits the translational machinery to nanos mRNA and promotes nanos translation. Through this mechanism, Dnd1 prevents somatic differentiation of PGCs and protects their totipotency. Our recent preliminary results reveal that Dnd1 is rapidly degraded in the oocyte by the ubiquitin- independent proteasome system. In order for Dnd1 to accumulate and promote nanos translation after fertilization, RNAs coding for proteasome activators must be separated from dnd1 and other germline specific maternal factors during the oocyte-to-embryo transition. We propose to study how this novel mRNA translocation event prepares for the initiation of PGC development after fertilization and investigate how RNAs coding for proteasome activators are separated from dnd1 and other germline specific maternal factors during the oocyte-to-embryo transition. Moreover, we have made an exciting finding that the first wave of PGC proliferation is regulated by maternal Dzip1. We will determine if Dzip1 regulates PGC proliferation via binding and modifying the activities of germline specific RNA-binding proteins. Furthermore, we will identify the zygotic transcriptional network that acts downstream of Dzip1 to control PGC proliferation. These works will make important contributions to our understanding of basic cell, reproductive, and developmental biology.