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一个关键前沿。除了基本的吸引力之外，阐明这些机制是实现生物医学目标的主要障碍，从理解器官发生中的先天性缺陷到组织工程器官培养。尽管对几个范例有了详细的了解，但我们目前只了解了器官惊人多样性的一小部分是如何形成的。为了扩大对形态发生谱系的了解，我们研究了果蝇卵泡--一个结构和几何上简单的器官--是如何经历组织伸长产生独特的椭圆形卵的。使用实时成像，我们发现了一种意想不到的形态发生行为，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，这种集体细胞迁移推动了器官的伸长。有趣的是，来自拓扑相似的脊椎动物系统的最新数据提出了平面极化旋转可能是保守的可能性。以卵泡旋转为代表的新的形态发生运动，其中PCP集体细胞迁移的无缘组织驱动其伸长，与常见的边缘器官的形态发生范例共享重要元素。它还提出了一些独特的特征，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组织延伸这一替代策略背后的机制。为此，我们将解决以下问题：1)。PCP在卵泡中是如何组织的，它独立于传统的PCP调节剂？围绕组织轴的集体迁移如何导致沿该轴的伸长？控制PCP旋转和组织伸长的分子机制是什么？这些问题的答案将揭示驱动形态发生的新原理和新机制，并推动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.