Project Summary Parasitic nematodes infect more than 150 million people worldwide and up to 1.3 billion people benefit from preventative treatment annually. Many parasitic nematodes require insect hosts for transmission to human hosts in their complex life cycles. We use a genetically tractable nematode Pristionchus pacificus that is associated with insects as a comparative model to study how diverse behaviors arise from a limited set of neurons. Our proposed research addresses a fundamental question on how nervous systems evolve to accommodate new behaviors, specifically how and which transcription factors are required to designate the developmental fates of chemosensory neurons in host- seeking behavior. We will use reverse genetics to target candidate transcriptional factors, known as terminal selector genes, as well as inducible transgenes to knock down neuronal function at the single cell level. We will also use forward genetics to investigate unbiasedly which genes are responsible to switch the preferences for taste and smell when the nematodes develop into reproductive adults or host-seeking infectious larvae. A detailed understanding of how neuronal remodeling affects chemosensation could reveal the basic blueprint for sensory neurons found in diverse nematodes, which could inform ways to disrupt the transmission of parasitic nematodes between insect and human hosts.