Inter-organ signals regulating body size, physiology anddevelopmental timing

调节身体大小、生理和发育时机的器官间信号 识别和表征调节器官的生理机制 在发育和成年过程中的沟通和功能对理解至关重要 在我们的有生之年，有多少重要的人类健康问题出现并加剧。 该提案概述了进一步确定关键信令系统特征的研究策略 调节关键和保守的生理过程。这些措施包括确定 由三个果蝇激活素样成员组成的信号网络如何影响转化生长因子-β 超级家族协调控制大脑、肌肉和脂肪的基本方面 细胞功能对营养等环境变量的响应 维持生理动态平衡的研究进展及神经内分泌机制 调节类固醇的产生和释放，也是为了应对各种内外 暗示，以适当的时间发育成熟。我们将使用各种各样的现代 生物学研究方法，包括遗传分析、神经元回路和活动 测绘、生物化学、光学/EM成像、代谢组学、时间和组织特异性 转录组鉴定以及染色质免疫沉淀实验，以 回答这些问题。对人类健康的影响：成功完成这些 AIMS将为两个非常保守的器官间信号如何提供新的见解 网络解析出对各种基本信息的特定控制和组合控制 细胞过程以产生比例适当的动物，这是优化的 在其特定的生态位中生存。预计这一知识将提供 用于理解更复杂但高度复杂的功能方面的有用范例 相关脊椎动物转化生长因子-β和神经内分泌信号系统，并将提供新的 对导致许多人类疾病的分子机制的洞察 包括肥胖、代谢综合征、肌肉萎缩、青春期疾病和衰老。

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.