Regulation of Drosophila Epithelial Polarity

描述（由申请人提供）：驱动形态发生的细胞机制是发育生物学的关键前沿。除了它们的基本魅力之外，阐明这些机制是从了解器官发生中的先天性缺陷到工程器官培养等生物医学目标的主要障碍。尽管我们对几个典型的例子有了详细的了解，但我们目前只了解器官惊人多样性的一小部分是如何形成的。为了扩大知识的形态发生剧目，我们研究如何果蝇卵泡，一个结构和几何简单的器官，经历了组织伸长，产生一个独特的椭圆形的鸡蛋。使用实时成像，我们发现了一个意想不到的形态发生行为，其中整个器官围绕其圆周轴执行几个完整的平面极化旋转。强有力的证据表明，这种集体细胞迁移驱动器官伸长。有趣的是，最近的数据从拓扑相似的脊椎动物系统提出的可能性，平面偏振旋转可能是保守的。新的形态发生运动代表卵泡旋转，其中PCP集体细胞迁移的“无边”组织驱动其伸长，共享重要的元素与熟悉的形态发生范例中的“边缘”器官。它还呈现出一些独特的特征，这些特征必须涉及新的生物学。我们将利用这一令人兴奋的发现来揭示这种替代组织延伸策略的机制。为此，我们将解决以下问题：1）。五氯苯酚在卵泡中是如何组织的，这与传统的五氯苯酚调节剂无关？2）。围绕组织轴的集体迁移如何导致沿该轴的沿着伸长？3）。什么分子机制控制PCP旋转和组织伸长？这些问题的答案将揭示驱动形态发生的新原理和机制，并使我们更全面地了解器官是如何形成的。

DESCRIPTION (provided by applicant): The cellular mechanisms that drive morphogenesis are a key frontier of Developmental Biology. Beyond their basic fascination, elucidating these mechanisms is a major obstacle to biomedical goals ranging from understanding congenital defects in organogenesis to engineered organ culture. Despite a detailed understanding of several paradigmatic examples, we currently understand how only a fraction of the astonishing diversity of organs take shape. To expand knowledge of the morphogenetic repertoire, we study how the Drosophila follicle, a structurally and geometrically simple organ, undergoes a tissue elongation to produce a distinctive oval egg. Using live imaging, we have discovered an unexpected morphogenetic behavior in which the entire organ executes several complete, planar-polarized rotations around its circumferential axis. Strong evidence indicates that this collective cell migration drives organ elongation. Intriguingly, recent data from topologically analogous vertebrate systems raise the possibility that planar-polarized rotation may be conserved. The new morphogenetic movement represented by follicle rotation, in which PCP collective cell migration of an 'edgeless' tissue drives its elongation, shares important elements with familiar morphogenetic paradigms in 'edged' organs. It also presents a number of distinctive features that must involve new biology. We will exploit this exciting discovery to uncover mechanisms underlying this alternative strategy of tissue extension. To do so, we will address the following questions: 1). How is PCP organized in the follicle, which is independent of conventional PCP regulators? 2). How does collective migration around a tissue axis lead to elongation along that axis? 3). What molecular mechanisms control PCP rotation and tissue elongation? The answers to these questions will reveal new principles and mechanisms that drive morphogenesis, and move us towards a more complete understanding of how organs are shaped.