Growth, and ultimately the size of an animal is regulated by the nervous system, which integrates genetically hardwired developmental processes together with the plastic process of continuous sensing of an animal's environmental condition and energy state. When growth or energy states are deregulated in humans, disorders such as cancer or obesity can result. How sensory inputs and integration of environmental information by the nervous system influences growth is poorly understood. C. elegans provides a tractable system for defining the molecular and neural basis of body size. The body size of C. elegans is partly regulated by sensory perception and food signals, suggesting that the sensory system regulates body size in response to changing environmental conditions. KIN-29, the C. elegans homolog of Salt-Inducible Kinase (SIK), is a key regulator of body size and food-related responses in C. elegans (1). KIN-29 acts in chemosensory neurons (CNs) to regulate chemoreceptor (CR) gene expression and body size. We believe that CR gene modulation in CNs underlies, at least in part, the ability of animals to correctly transduce food-derived signals to modulate body-size. To further dissect the KIN-29 signaling pathways by which food signals are integrated to modulate behavior and development, we are using multiple parallel strategies. First, we are defining the particular CNs that require KIN-29 for regulating body size. Secondly, we are identifying additional novel genes acting in the KIN-29-mediated body size pathway. Thirdly, in collaboration with the NCGR, we are sequencing polyA-tagged mRNA isolated from two sensory neuron types of adult wild-type and kin-29 mutants. Expression profiling of functionally different sensory neuron types will not only identify novel genes expressed in sensory neurons, but will pave the way for making a complete catalog of expression profiles of each individual sensory neuron type of C. elegans. Finally, we are examining a KIN-29-dependent CR gene whose expression in the ADL chemosensory neurons is acutely altered by the presence and absence of food in adult animals. We take advantage of this observation by identifying the molecular components and neurons by which food signals alter CR gene expression using genetic screens. Together these results will reveal the complex signaling pathways by which environmental information is integrated by the nervous system to modulate body size in animals. (1) Lanjuin et al. 2002; Van der Linden et al. 2007, 2008.