KIN-29 SIK SIGNALING THE THEREGULATION OF FOOD-RELATED BEHAVIORS & DEVELOPMENT

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 生长，最终动物的大小是由神经系统调节的，神经系统将遗传上固定的发育过程与持续感知动物环境条件和能量状态的可塑性过程结合在一起。当人类的生长或能量状态被解除管制时，可能会导致癌症或肥胖症等疾病。神经系统的感觉输入和环境信息的整合如何影响生长还知之甚少。线虫提供了一个易于处理的系统来定义身体大小的分子和神经基础。线虫的身体大小部分受感官知觉和食物信号的调节，这表明感官系统调节身体大小以应对不断变化的环境条件。我们以前的工作表明，KIN-29盐诱导激酶(SIK)通路作用于化学感觉神经元(CNS)，调节感觉基因的表达、身体大小和与食物相关的行为。我们推测，对感觉基因表达的正确调节对于适当地获取环境信号是必要的，从而调节感觉输入到对身体大小重要的通路。SIK功能参与摄食/禁食反应，是TGFbeta途径的调节因子，参与哺乳动物和线虫的生长控制。从人类到线虫的SIK功能的保守为探索感觉信息如何参与细胞生长和身体大小提供了机会。我们利用遗传学和基因组学方法在线虫中提出以下建议：目的1)定义通过KIN-29调节身体大小的感觉神经元的亚群(S)；目的2)定义由KIN-29调控的一整套感觉基因；以及目的3)寻找在KIN-29介导的身体大小途径中起作用的新基因。对线虫保守生物途径的研究将有助于我们理解人类参与健康和疾病的途径。

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.