In this grant, we propose to understand the molecular mechanisms of dendrite morphogenesis and function. Dendrite morphogenesis determines the connectivity of neurons. We are using a model cell (PVD in C elegans) to study this question. PVD is a proprioceptive neuron that senses muscle contraction and regulates animal movement. In our previous work, we identified the extracellular ligands and their receptor on PVD that guide the dendrite growth and branching. Here, we propose to understand how the receptor-ligand interaction triggers signaling mechanisms and leads to cytoskeletal modifications which eventually drives the morphogenesis events. We will also study how the neurons regulate receptor signaling using a drug target protein called KPC-1 to control guidance decisions. We will also understand how the PVD neurons sense muscle contraction using a putative mechanosensitive channel and how it regulates neuromuscular activity through a surprising neural circuit feedback mechanism. Through these experiments, we will gain insights in the molecular logic of dendrite development. We will identify novel mechanosensitive channels that are important for body movement regulation.
Dendrites are highly branched neuronal processes that serve as the ?antenna? of neurons to gather information. Understanding the molecular mechanisms underlying dendrite growth and branching will provide the basis for developing new strategies for combating developmental neurological diseases and for slowing down the progression of neurodegenerative diseases. In addition, such knowledge will be helpful for developing strategies to promote the regeneration of neural circuits after stroke.
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