Project Summary The communication among different tissues (or organs), such as the gut-brain axis, is crucial in regulating animal physiology and developmental decisions. The nematode Caenorhabditis elegans enters a non-feeding, developmentally arrested dauer stage to cope with the harsh environments, such as food shortage and over- population. The dauer decision is regulated by the multiple pathways (insulin, growth factor, and hormone), involving the nervous system, XXX neuroendocrine cells, and intestine. Previous research has established C. elegans as a model organism to study stress-responsive development, but tissue-specific regulation of dauer development remains unclear. In particular, little is known about how nervous system coordinates with the intestine to integrate the signaling pathways and make a whole-organism dauer decision. The proposed aims focus on providing a systematic study of how different tissues communicate through multiple signaling pathways and coordinately regulate the dauer decision using molecular genetics tools recently developed in the sponsor lab. To achieve this goal, Aim 1 will focus on investigating the general roles of each tissue during dauer development and build models for the regulatory network; Aim 2 will focus on temporal participation of each tissue and each pathway in dauer decision initiation and execution, further developing precise circuits of dauer regulation. Altogether, the proposed aims will expand the current knowledge of molecular mechanisms underlying developmental timing of commitment to diapause in response to environmental stress. Using C. elegans dauer decision as a model, the proposed project will contribute to better understanding of the inter-tissue coordination, particularly in brain-gut communication, during the developmental decision making process.

Project Narrative The bidirectional signaling in between gastrointestinal tract and the brain, termed the gut-brain axis, is crucial to the mental and physical health of individuals. Even though the gut-brain axis is still in the early stage of study, increasing evidence has shown that disruptions of gut-brain communications could cause disorders in metabolism and immunity, leading to severe and complicated conditions such as irritable bowel syndrome (IBS) or Parkinson disease. Using C. elegans dauer as a model, the proposed research will investigate gut- brain communication in regulating a stress-responsive developmental decision, further contributing to current knowledge of inter-tissue (organ) communication in controlling animal physiology.