Our framework of understanding communication within the nervous system has traditionally focused on neurotransmitter-based synaptic transmission, thereby leaving out the importance of neuropeptides and their cognate receptors as modulatory elements. It is becoming increasingly clear that neuropeptides regulate important neurological processes by mediating communication between neurons and across tissues. Accordingly, neuropeptides have been implicated a broad array of neurological disorders including neurodegenerative diseases such as Alzheimer?s and Parkinson?s Disease. However, the precise molecular mechanisms that explain how neuropeptides participate in neurotransmission are not well understood. The overarching goal of this proposal is to use the roundworm Caenorhabditis elegans as a model organism to further our understanding of how neuropeptides communicate information within a densely connected nervous system. In this proposal, I plan to delineate a neuropeptide-based signaling mechanism that transmits chemosensory information in order to make an important developmental decision. Specifically, this proposal will study how neuropeptides participate in the dauer exit decision, which is an irreversible developmental decision in which C. elegans that have previously entered the stress-resistant diapause state (termed dauer) choose to exit from that state and return to their reproductive life cycle as late stage larval worms.
Aim 1 of this proposal seeks to broadly identify and characterize neuropeptide genes that are essential for the dauer exit decision.
Aim 2 takes a single neuron approach and focuses on a specific chemosensory neuron essential for dauer exit: the ASJ neuron. In this aim, I will identify which neuropeptide(s) ASJ relies on in order to mediate the dauer exit decision. Finally, in Aim 3, I examine how neuropeptides themselves are regulated in response to appropriate external stimuli by using reporter technology to in-depth study the regulation of one particular neuropeptide gene in the ASJ neuron demonstrated to be important for dauer exit. Collectively, all three aims will portray a clearer picture of how neuropeptides serve as a bridge between chemosensory inputs and downstream developmental programs in an organism such as C. elegans.
Neuropeptides are a conserved class of neuromodulators implicated in various neurological disorders ranging from chronic pain to neurodegenerative diseases. While their role in mediating diverse neuronal processes is well-appreciated, the precise molecular mechanisms that govern how neuropeptides communicate information across neurons and tissues, as well as how neuropeptides themselves are regulated in response to environmental flux, remains poorly understood. Using C. elegans as a model organism, I will elucidate a neuropeptidergic signaling pathway that governs an important C. elegans developmental decision, which will significantly enhance our molecular understanding of how neuropeptides fit within the framework of nervous system communication.
