Developmental control of cell polarity in vertebrate embryos.

我们实验室的一个长期目标是了解细胞极性和 脊椎动物胚胎的组织形态发生。这里我们的重点是平面细胞极性(PCP)信号级联，这是一种控制纤毛形成和细胞运动的分子机制，称为会聚延伸。纤毛是以微管为基础的细胞突起，在广泛的人类病理中起着重要作用。例如，纤毛细胞产生的定向液体流动对 神经系统、肾脏、生殖系统和呼吸道的功能。这些“纤毛疾病”包括囊性肾脏疾病、肥胖综合征、不孕不育、部位异常和中枢神经系统的形态缺陷。脊椎动物(包括人类)的神经管闭合需要会聚的伸展细胞运动。这项提案将研究PCP蛋白FRITZ在纤毛发生和汇聚延伸中的作用。在纤毛发生过程中，我们会问Fritz在微管的多聚谷氨酰化和Septin细胞骨架的组织中起什么作用。在融合延伸过程中，我们将询问FRITZ如何控制细胞行为，包括膜突起活动和中心体定位。总之，这些实验将帮助我们理解PCP信号如何影响汇聚延伸和纤毛发生等不同的细胞过程。

A long-term goal of our lab is to understand the molecular basis of cell polarity and tissue morphogenesis in vertebrate embryos. Our focus here is on the Planar Cell Polarity (PCP) signaling cascade, a molecular mechanism that governs both the formation of cilia and cell movements called convergent extension. Cilia are microtubule-based projections of the cell with important roles in a wide range of human pathologies. For example, the directed fluid flow generated by ciliated cells is crucial for the function of the nervous system, the kidney, the reproductive systems, and the airway. Such “ciliopathies” include cystic kidney diseases, obesity syndromes, infertility, situs abnormalities, and morphological defects on the central nervous system. Convergent extension cell movements are required for neural tube closure in vertebrates, including humans. This proposal will examine the role of the PCP protein, Fritz, in ciliogenesis and convergent extension. During ciliogenesis, we will ask what role Fritz plays in polyglutamylation of microtubules and in the organization of the septin cytoskeleton. During convergent extension, we will ask how Fritz controls cell behaviors, including membrane protrusive activity and centrosomal positioning. Together, these experiments will help us to understand how PCP signaling influences such diverse cellular processes as convergent extension and ciliogenesis.