Inter-organ signals regulating body size, physiology anddevelopmental timing

调节身体大小、生理和发育时间的器官间信号 识别和表征调节器官的生理机制 发育和成年期的沟通和功能对于理解 在我们的一生中，有多少重要的人类健康问题出现和加剧。 该提案概述了进一步表征关键信号系统的研究策略 调节重要的和保守的生理过程。其中包括确定 三个果蝇激活素样TGF-β成员的信号网络 超家族协调控制大脑、肌肉和脂肪体基本方面 细胞功能对环境变量的反应，如营养， 维持生理稳态的神经内分泌机制 调节类固醇的产生和释放，也响应各种内部和外部 提示，以正确的时间发育成熟。我们将使用各种现代 生物学研究方法，包括遗传分析、神经回路和活动 映射、生物化学、光学/EM成像、代谢组学、时间和组织特异性 转录组表征以及染色质免疫沉淀实验， 回答这些问题对人类健康的影响：成功完成这些 目的将提供新的见解如何两个非常保守的器官间信号传导， 网络解析出特定的，以及组合控制，在各种基本的， 细胞过程，以产生适当比例的动物，这是优化， 在其特定的生态位中生存。预计这些知识将提供 有用的范例，了解功能方面的更复杂的，但高度 相关的脊椎动物TGF-β和神经内分泌信号系统，并将提供新的 深入了解导致许多人类疾病的分子机制 包括肥胖、代谢综合征、肌肉萎缩、青春期紊乱和衰老。

Inter-organ signals that regulate body size, physiology and developmental timing Identifying and characterizing physiologic mechanisms that regulate organ communication and function during development and adulthood is vital for understanding how many important human health problems arise and intensify during our lifetimes. This proposal outlines a research strategy to further characterize key signaling systems that regulate critical and conserved physiological processes. These include determining how a signaling network of three Drosophila Activin-like members of the TGF-beta superfamily coordinately control fundamental aspects of brain, muscle, and fatbody cellular function in response to environmental variables such as nutrition during development to maintain physiologic homeostasis and how neuroendocrine mechanisms regulate steroid production and release, also in response to various internal and external cues, to properly time developmental maturation. We will use a wide variety of modern biological investigative methods including genetic analysis, neuronal circuit and activity mapping, biochemistry, optical/EM imaging, metabolomics, temporal and tissue specific transcriptome characterization as well as chromatin immunoprecipitation experiments, to answer these questions. Impact on human health: The successful completion of these aims will provide novel insight into how an two very conserved inter-organ signaling networks parse out specific, as well as combinatorial control, over various fundamental cellular processes to produce a properly proportioned animal, that is optimized for survival in its particular ecological niche. It is expected that this knowledge will provide useful paradigms for understanding functional aspects of the more complex, but highly related vertebrate TGF-beta and neuroendocrine signaling systems, and will afford novel insights into molecular mechanisms that contribute to a number of human disorders including obesity, metabolic syndrome, muscle wasting, pubertal disorders and ageing.