Animals must be able to alter their development and behavior in response to changing environmental conditions and on the basis of prior experience. This developmental and behavioral plasticity is mediated by changes in gene expression. Our goal is to understand the mechanisms by which environmental signals are transduced and integrated to modulate changes in sensory gene expression, and ultimately, in behavior. C. elegans responds to conditions of overcrowding, limited food and high temperature by arresting development as a dauer larva. A primary signal triggering entry into the dauer stage is high levels of secreted dauer pheromone. We and others showed previously that exposure to low levels of crude dauer pheromone alters the expression of a subset of putative G-protein coupled chemosensory receptor genes in the ASI chemosensory neurons (Nolan et al., 2002; Peckol et al., 1999). We have now shown that similar to crude dauer pheromone, low-levels of chemically synthesized dauer pheromone (daumone: Jeong et al., 2005) reversibly repress expression of the str-3 chemoreceptor gene in ASI. Repression of str-3 expression upon low levels of daumone exposure can be initiated only at the L1 stage, but expression is restored upon removal of daumone at any developmental stage. To identify the signaling pathways and genes required for this environmentally-regulated gene expression, we performed a genetic screen as well as a candidate gene search. We identified cmk-1 (Ca2+/calmodulin-dependent protein kinase I :CaM Kinase I) and ckk-1 ( CaM kinase kinase) as genes that are required to downregulate str-3 expression upon daumone exposure. In addition, we tested crh-1 (cyclic AMP response element binding protein :CREB) ,a putative target of the CaMK cascade and showed that crh-1 is required for str-3 expression even in the absence of daumone. Thus, the CAMK cascade may act to inhibit CRH-1 function upon daumone exposure. Surprisingly, neither cmk-1 nor crh-1 appear to act cell-autonomously to regulate str-3 expression in the ASI neurons. Currently, we are investigating the spatial requirements of cmk-1 and crh-1 function in the regulation of str-3 expression. We are also cloning additional genes identified in our genetic screen, and identifying the cis-regulatory elements required to confer daumone-mediated regulation.