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传导

• 批准号: RGPIN-2018-05467
• 负责人: ChinSang, Ian
• 金额: $ 3.64万
• 依托单位: Queen's University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=690054
• 关键词: Neuronal; Epidermal; Signaling; during; C.

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.*****

C.过程中的神经元和表皮信号传导受精后，卵子开始分裂，形成一个细胞球。这个无定形的细胞球是如何形成蠕虫、苍蝇甚至人类的？这个迷人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。 我的研究计划使用了最先进的显微镜技术，结合了C语言的强大功能。elegans遗传学来了解形态发生运动。我对一种名为klp-20的基因感到兴奋，它编码一种类似驱动蛋白的马达蛋白，这种蛋白是正常表皮形态发生所必需的。KLP-20是哺乳动物中进化保守的驱动蛋白，称为KIF 3A。 驱动蛋白是在细胞内移动货物的分子马达。 KLP-20/KIF 3A已被证明与另外两种蛋白质KLP-11/KIF 3B和KAP-1/KAP 3形成复合物，这种异源三聚体复合物被称为驱动蛋白-II，最好的特征作用是称为鞭毛内转运（IFT）的过程，以帮助建立纤毛。这些纤毛被认为是细胞天线，检测来自环境的细胞外信号。我们提供的证据表明，KLP-20/KIF 3A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，两个彼此非常接近的组织，如何相互交流以促进正常发育。 我的建议是新颖的，因为我的研究计划将为KLP-20/KIF 3A提供新的角色。我们建议详细描述C发生了什么。当你废除KLP-20的所有功能或废除它在某些细胞或组织中的功能时， 我们将测试一个假设，即KLP-20马达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马达蛋白的新型蛋白质-蛋白质相互作用。 这项建议将直接受益于至少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础科学知识，这些知识具有广泛的学术和工业应用。