This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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. C. elegans body size is partly regulated by sensory perception and food signals, suggesting that the sensory system regulates body size in response to changing environmental conditions. Our previous work demonstrates that the KIN-29 Salt-Inducible Kinase (SIK) pathways acts in the chemosensory neurons (CNs) to regulate sensory gene expression, body size and food-related behaviors. We postulate that correct regulation of sensory gene expression is necessary to appropriately acquire environmental signals, thereby regulating sensory inputs into pathways important for body size. SIK function is involved in feeding/fasting responses, and is a regulator of the TGFbeta pathway implicated in growth control in both mammals and in C. elegans. Conservation of SIK function from humans to C. elegans offers the opportunity to explore how sensory information may be involved in cell growth and body size. We use genetic and genomic approaches in C. elegans to propose the following:
Aim 1) to define the subset(s) of sensory neurons that regulate body size via KIN-29;
Aim 2) define the complete set of sensory genes regulated by KIN-29;
and Aim 3) to identify novel genes acting in the KIN-29-mediated body size pathway. The study of conserved biological pathways in C. elegans will inform our understanding of human pathways involved in health and disease.
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