Grant: Discovery Grants Program - Individual

Neuronal and Epidermal Signaling during C. elegans MorphogenesisAfter 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.