Cytokinesis and RNA segregation in zebrafish development

项目总结/摘要 在许多动物物种中，生殖细胞命运的决定取决于种质的母系遗传， 一种由核糖核颗粒（RNP）组成并富含细胞骨架成分的特化细胞质。胚芽 血浆RNP通常作为卵内的颗粒遗传，其在早期胚胎发生期间变成 聚集成大团。这些细胞被分离成原始生殖细胞（PGCs）， 被认为促进生殖细胞转录程序的启动。在斑马鱼中，就像在其他一些 在脊椎动物物种中，种质RNP的聚集和分离与细胞分裂相关联。斑马鱼胚 已经证明，在这种生物体中，原生质是生殖细胞诱导所必需的并且是足够的。我们有 先前描述的细胞分裂过程中的特定步骤，导致种质RNP募集到细胞中， 在最初的几个循环中进行犁沟，随后在犁沟远端进行压实。这些步骤需要 种质RNP聚集度逐渐增加，导致4个大种质的稳定 群众这些质量是遗传的原始生殖细胞，最终分散通过细胞质在PGC 规范.我们的总体假设是，种质RNP聚集是由适应介导的 依赖于动态的、易兴奋的皮层和流体之间的相互作用， RNP和相关的内在无序蛋白质（IDP）的类相位特性。在目标1中，我们 解决了兴奋性肌动球蛋白网络的调节如何介导种质RNP运动， 聚集，并将研究染色体乘客复合物（CPC）的因子组分的功能 在细胞骨架网络动力学和种质RNP锚定。在目标2中，我们将研究 分离的种质RNP作为有序的超分子结构在沟，以及在生殖的作用， 先前未表征的IDP Bucky球2样的血浆分离。生殖细胞的命运 多能性和癌症的特征，我们的研究将提供新的知识，不仅适用于 还有细胞重编程和癌症生物学。对无膜的理解 通过流体相行为的区室化将提供与以下相关的其他基本见解： 人类生物学和疾病。

Project Summary / Abstract In many animal species, germ cell fate determination depends on the maternal inheritance of the germ plasm, a specialized cytoplasm composed of ribonucleoparticles (RNPs) and enriched in cytoskeletal elements. Germ plasm RNPs are typically inherited as particles within the egg, which during early embryogenesis become aggregated into large masses. These become segregated into primordial germ cells (PGCs), where they are thought to promote the initiation of the germ cell transcriptional program. In zebrafish, as in a number of other vertebrate species, gathering and segregation of germ plasm RNPs is coupled to cell division. Zebrafish germ plasm has been shown to be required and sufficient for germ cell induction in this organism. We have previously delineated specific steps during cell division that result in germ plasm RNP recruitment to the furrows for the first several cycles, with subsequent compaction at the furrow distal ends. These steps entail a gradual increase in germ plasm RNP aggregation and result in the stabilization of four large germ plasm masses. These masses are inherited by PGCs, to eventually disperse through the cytoplasm during PGC specification. Our overarching hypothesis is that germ plasm RNP aggregation is mediated by adaptations of the cellular machinery, relying on the interaction between a dynamic, excitable cortex and fluid phase-like properties of RNPs and associated intrinsically disordered proteins (IDPs). In Aim 1, we will address how the regulation of an excitable actomyosin network mediates germ plasm RNP movement and aggregation, and will study the function of factors components of the Chromosomal Passenger Complex (CPC) in cytoskeletal network dynamics and germ plasm RNP anchoring. In Aim 2, we will study the behavior of segregating germ plasm RNPs as ordered supramolecular structures at the furrows, as well as the role in germ plasm segregation of the previously uncharacterized IDP Bucky ball 2-like. The germ cell fate shares characteristics with pluripotency and cancer, and our studies will provide new knowledge applicable not only to reproduction but also cell reprogramming and cancer biology. Understanding of membrane-less compartmentalization through fluid phase behavior will provide additional fundamental insights relevant to human biology and disease.