Using Drosophila eclosion to genetically dissect how central and peripheral clocks and the endocrine system interact to time behaviour

对于动物来说，对不同身体系统的发育和生理活动进行定时和同步，并相应地调整行为是至关重要的。不同身体系统和行为的定时和同步需要计时器（由中枢和外周内源性时钟代表）和集成通信系统（由（神经）内分泌系统代表）。然而，我们对复杂的神经元和内分泌通路以及内源性时钟和神经内分泌系统相互作用的潜在分子和细胞信号机制知之甚少。这些知识可以为理解和治疗相关的发育障碍和昼夜节律功能障碍提供线索，包括生育能力受损、睡眠障碍和精神问题，这些都可能导致这种综合时间的长期中断。该项目的目的是剖析发育和昼夜节律计时器与神经内分泌系统之间的相互作用，并开始描述计时行为背后的细胞和分子信号传导原理。这里的主要焦点是肽和类固醇激素信号传导及其昼夜节律控制之间的相互作用。我们还旨在找出大脑中昼夜节律和发育信号与特定行为的时间相结合的地方。这种特殊的行为会使果蝇羽化。果蝇似乎是一个非常适合这个项目的模型系统，因为它在遗传和实验上都很容易处理，并且拥有相对较少的个体可识别的神经元。从长远来看，这提供了从分子到系统水平完整地破译中枢和外周时钟与靶组织之间的神经元和激素联系的可能性。羽化是很合适的，因为它是由发育和昼夜节律计时器计时的，它的时间是在肽和类固醇激素的控制下。从动物学的角度来看，了解神经元-内分泌网络定时羽化的结构是非常有趣的，因为正确的羽化时间对昆虫和其他节肢动物的生存和健康至关重要，它们代表了我们星球上绝大多数动物。

For animals, it is vitally important to time and synchronise development and physiological activity of the different body systems and to adjust behaviour accordingly. The timing and synchronisation of different body systems and behaviour requires both a timer (represented by central and peripheral endogenous clocks) and an integrating communication system (represented by the (neuro)endocrine system). Yet, we know astonishingly little about the complex neuronal and endocrine pathways and underlying molecular and cellular signalling mechanisms by which endogenous clocks and neuroendocrine systems interact with each other. Such knowledge could provide a handle to understand and treat associated developmental disorders and circadian dysfunctions including impaired fertility, sleep disturbances and psychiatric problems that can result from long-term disruption of this integrated timing.The aim of this project is to dissect the interactions between developmental and circadian timers and the neuroendocrine system, and to start characterising cellular and molecular signalling principles underlying timed behaviour. A main focus here is on the interplay between peptide and steroid hormone signalling and its circadian control. We also aim to find out where in the brain circadian and developmental signals are integrated to time a specific behaviour.This specific behaviour will be the eclosion of the fruit fly Drosophila. The fruit fly appears a highly suited model system for this project as it is genetically and experimentally well tractable, and possesses a relatively low number of individually identifiable neurons. This in the long range offers the possibility to in completeness decipher neuronal and hormonal connections between central and peripheral clocks and target tissues from the molecular to the systemic level. Eclosion is well suited as it is timed by developmental and circadian timers, and its timing is under control of both peptide and steroid hormones. From a zoological point of view, understanding the architecture of the neuronal-endocrine network timing eclosion is of great interest since correct eclosion timing is most critical for the survival and fitness of insects and other arthropods, which represent the vast majority of animals on our planet.