权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Maternal control of germline development

种系发育的母体控制

基本信息

批准号：
10625487
负责人：
Jing Yang
金额：
$ 38.31万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2025-05-31
项目状态：
未结题

项目摘要

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.

摘要原始生殖细胞（PGCs）是配子的前体。PGC开发缺陷导致生殖细胞减少或消除，最终导致人类不育，这影响了10-15%的人，夫妻。在发育过程中，PGCs比性腺的形成早得多。PGCs必须设法在无保护的躯体环境中生存很长时间，然后迁移很长时间找到性腺的距离在早期阶段，PGCs的特化及其增殖至关重要以确保足够数量的PGCs能够到达性腺并分化成配子。大大量文献表明，在迁移到性腺之前，PGC的发育严重依赖于翻译和翻译后调节机制。了解PGC开发如何因此，在翻译和翻译后水平上操作的基因与人类生殖高度相关。健康我的实验室以非洲爪蟾为模型研究早期PGC的发展。我们最近报道母亲死亡末端1（Dnd 1）对于卵母细胞中mRNA的不对称定位是重要的。后在受精过程中，Dnd 1将翻译机器募集到nanos mRNA并促进nanos翻译。通过这种机制，Dnd 1阻止PGCs的体细胞分化并保护其全能性。我们最近的初步结果表明，Dnd 1在卵母细胞中被泛素- 独立的蛋白酶体系统。为了使Dnd 1积累并促进纳米翻译，受精，编码蛋白酶体激活剂的RNA必须从dnd 1和其他种系中分离出来，卵母细胞向胚胎过渡期间的特定母体因素。我们打算研究这部小说 mRNA易位事件为受精后PGC发育的启动做准备，并研究如何从dnd 1和其他生殖系特异性母体中分离编码蛋白酶体激活剂的RNA 卵母细胞向胚胎过渡期间的因素。此外，我们有一个令人兴奋的发现， PGC的增殖受母体Dzip 1的调控。我们将确定Dzip 1是否调节PGC 通过结合和修饰生殖系特异性RNA结合蛋白的活性来促进增殖。此外，我们将确定合子转录网络的行为下游的Dzip 1，以控制 PGC增殖。这些工作将对我们理解基本细胞，生殖和发育生物学。