Control of Early Embryonic Cell Polarity in a Model Deuterostome

描述（申请人提供）：提出一系列实验来分析海胆切割胚胎模型后口动物早期细胞极性的性质和生物学功能。动物王国根据胚胎的发育方式分为两大类。棘皮动物，包括海胆，像低等和高等脊索动物一样发育，而其他遗传模式生物，包括苍蝇和蠕虫，对它们的发育进行了大量研究，发育非常不同。这些低等生物的胚胎在受精和早期卵裂分裂时表现出非常深刻的细胞和胚胎极性，而这种极性在后口动物中尚未得到很好的研究。虽然棘皮动物胚胎具有典型的卵裂，例如，由两层4个细胞组成的8细胞胚胎，但这种胚胎在16细胞阶段也表现出在植物极形成的小微粒，其发育作用是原肠胚形成的信号细胞和注定形成幼虫骨骼的细胞，已经得到了很好的研究。较少被分析的是这个早期胚胎在最早的卵裂分裂时的细胞极性。我们的初步工作有力地表明，在棘皮动物的第一次细胞分裂中，被称为Par复合物的相同极性的蛋白质像在原造口动物中一样是极化的，并且极性是功能性的。我们提出的问题是Par复合物蛋白是如何以极化的方式固定在细胞皮层上的，以及它们的功能是如何在这个模型后口动物中被调节的。

DESCRIPTION (provided by applicant): A series of experiments are proposed to analyze the nature and biological function of early cell polarity in a model deuterostome, the sea urchin cleaving embryo. The animal kingdom is divided into two major groups based on how their embryos develop. Echinoderms, including sea urchins, develop like lower and higher chordates whereas other genetic model organisms heavily studied for their development, including flies and worms, develop very differently. The embryos of these lower organisms exhibit very profound cellular and embryonic polarity upon fertilization and early cleavage divisions whereas such polarity has not been well investigated in the deuterostomes. While the echinoderm embryo has stereotypical cleavage, with for instance an eight cell embryo composed of two tiers of four cells, this embryo also exhibits formation of small micromeres at the vegetal pole at the 16 cell stage whose developmental roles as signaling cells for gastrulation and as cells fated to form the larval skeleton are well studied. Less well analyzed is the cellular polarity of this early embryo at the earliest cleavage divisions. Our preliminary work strongly suggests that the same polarity proteins, termed the Par complex, are polarized, as in the protostomes, at the first cell division in echinoderms and that the polarity is functional. We ask questions in this proposal about how the Par complex proteins are anchored to the cell cortex in a polarized manner and how their functioning is regulated in this model deuterostome. PUBLIC HEALTH RELEVANCE: The research proposed in this application deals with the earliest stages of an embryo's development. We are studying the formation of early cell polarity after fertilization and the first cell divisions in a model organism closely related to vertebrates and findings from this research are directly relevant to the way in which humans develop.