Neuronal and Epidermal Signaling during C. elegans Morphogenesis

秀丽隐杆线虫形态发生过程中的神经元和表皮信号***受精后，卵子开始分裂形成细胞球。这个无定形的细胞球是如何形成蠕虫、苍蝇甚至人类的？这种迷人的发育过程被称为形态发生——形状和形态的变化。我的实验室的长期目标是了解在细胞改变形状和迁移到不同位置时调节细胞行为的分子。我使用遗传模式生物秀丽隐杆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结合秀丽隐杆线虫遗传学的惊人力量来了解形态发生运动。我对一种名为klp-20的基因感到兴奋，它编码一种类似运动蛋白的运动蛋白，这种蛋白是正常表皮形态发生所必需的。KLP-20是一种进化保守的运动蛋白，在哺乳动物中被称为KIF3A。运动蛋白是在细胞内运送货物的分子马达。KLP-20/KIF3A与另外两种蛋白KLP-11/KIF3B和KAP-1/KAP3形成复合物，这种异三聚体复合物被称为Kinesin-II，最具特征的作用是一种称为鞭毛内运输（IFT）的过程，以帮助构建纤毛。这些纤毛被认为是“蜂窝天线”，可以检测来自环境的细胞外信号。我们提供的证据表明，KLP-20/KIF3A具有独立于IFT的作用，KLP-20可能参与从神经系统到表皮的信号传递。由于klp-20突变体表皮形态发生异常，我们惊讶地发现klp-20在神经系统而不是表皮细胞中表达。我对神经元和表皮这两个相互靠近的组织如何相互沟通以促进正常发育很感兴趣。我的建议是新颖的，因为我的研究项目将为KLP-20/KIF3A提供新的作用。我们建议详细描述当您取消所有KLP-20功能或取消其在某些细胞或组织中的功能时，秀丽隐杆线虫的发育会发生什么。我们将测试一个假设，即KLP-20运动蛋白提供从神经元到表皮的信号，确定mirna是否构成信号的一部分，最后我们计划确定与KLP-20运动蛋白的新蛋白-蛋白相互作用。本提案将直接惠及至少5名研究生和几名本科生。获得的结果将有助于细胞生物学的基础科学知识，具有广泛的学术和工业应用。*****

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.*****