Neuronal and Epidermal Signaling during C. elegans Morphogenesis

线虫形态发生过程中的神经元和表皮信号*受精后，卵子开始分裂，形成一团细胞。这种无定形的细胞球体是如何形成蠕虫、苍蝇甚至人类的呢？这一令人着迷的发育过程被称为形态发生--形状和形式的变化。我的实验室的长期目标是了解当细胞改变形状并迁移到不同位置时，调节细胞行为的分子。我使用遗传模型生物秀丽线虫来研究细胞形状变化和运动的简单例子。我的研究计划使用最先进的显微镜和线虫遗传学的惊人力量来理解形态发生运动。我对一种名为KLP-20的基因感到兴奋，它编码一种运动蛋白样的运动蛋白，这是正常的表皮形态发生所必需的。KLP-20是一种进化保守的动蛋白，在哺乳动物中被称为KIF3A。动蛋白是一种分子马达，可以在细胞内移动货物。KLP-20/KIF3A已被证明与另外两种蛋白质KLP-11/KIF3B和KAP-1/KAP3形成复合体，这种异源三聚体复合体被称为Kinesin-II，最典型的作用是一种被称为鞭毛内转运(IFT)的过程，以帮助建立纤毛。这些纤毛被认为是探测来自环境的细胞外信号的“细胞天线”。我们提供的证据表明，KLP-20/KIF3A具有独立于IFT的作用，并且KLP-20可能参与将信号从神经系统传递到表皮。由于KLP-20突变体具有异常的表皮形态发生，我们惊讶地发现KLP-20在神经系统中表达，而不是在表皮细胞中表达。我感兴趣的是神经元和表皮这两个彼此接近的组织是如何相互沟通以实现正常发育的。我的建议是新颖的，因为我的研究计划将为KLP-20/KIF3A提供新的角色。我们建议详细描述当你取消所有KLP-20功能或取消其在某些细胞或组织中的功能时，对线虫发育的影响。我们将检验一个假设，即KLP-20马达蛋白提供来自神经元的信号到表皮，确定miRNAs是否构成该信号的一部分，最后我们计划确定新的蛋白质-蛋白质与KLP-20马达蛋白的相互作用。这项提议将直接惠及至少5名研究生和几名本科生。所获得的结果将有助于细胞生物学的基本科学知识，细胞生物学在学术和工业上都有广泛的应用。

Neuronal and Epidermal Signaling during C. elegans Morphogenesis***After fertilization, the egg starts to divide to form a ball of cells. How does this amorphous ball of cells form into a worm, fly or even a human being? This fascinating developmental process is called morphogenesis-the change in shape and form. My lab's long-term goals are to understand the molecules that regulate the behaviour of cells as they change their shape and migrate to different locations. I use the genetic model organism Caenorhabditis elegans to study simple examples of cell shape changes and movements. My research proposal uses state of the art microscopy combined with the awesome power of C. elegans genetics to understand morphogenetic movements. I am excited about a gene called klp-20 that encodes a kinesin like motor protein that is required for proper epidermal morphogenesis. KLP-20 is an evolutionary conserved kinesin known as KIF3A in mammals. Kinesins are molecular motors that move cargo inside of cells. KLP-20/KIF3A has been shown to work in a complex with two other proteins KLP-11/KIF3B and KAP-1/KAP3, this heterotrimeric complex is called Kinesin-II and the best characterized role is a process called intraflagella transport (IFT) to help build cilia. These cilia are thought to serve as ‘cellular antennas' that detects extracellular signals from the environment. We provide evidence to show that KLP-20/KIF3A has roles independent of the IFT and that KLP-20 may be involved in transmitting signals from the nervous system to the epidermis. Since klp-20 mutants have abnormal epidermal morphogenesis we were surprised to find that KLP-20 is expressed in the nervous system and not in the epidermal cells. I am interested in how the neurons and the epidermis, two tissues that are in close proximity to each other, communicate with each other for proper development. My proposal is novel as my research program will provide new roles for KLP-20/KIF3A. We propose to characterize in detail what happens to C. elegans development when you abolish all of KLP-20 function or abolish its function in certain cells or tissues. We will test a hypothesis that the KLP-20 motor protein provides signals from the neurons to the epidermis, determine if miRNAs make up part of the signal, and finally we plan to identify novel protein-protein interactions with the KLP-20 motor protein. This proposal will directly benefit at least 5 graduate students and several undergraduate students. The results obtained will contribute to the basic scientific knowledge of cell biology which has a wide variety of academic and industrial applications.*****