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计时和同步，并相应地调整行为是至关重要的。不同身体系统和行为的计时和同步既需要计时器(由中央和外周内源性时钟代表)，也需要一个整合的通讯系统(由(神经)内分泌系统代表)。然而，令人惊讶的是，我们对内源性时钟和神经内分泌系统相互作用的复杂神经和内分泌途径以及潜在的分子和细胞信号机制知之甚少。这些知识可以提供一种句柄来理解和治疗相关的发育障碍和昼夜节律功能障碍，包括生育力受损、睡眠障碍和精神问题，这些可能是由于长期扰乱这种综合计时而导致的。这个项目的目的是剖析发育和昼夜节律计时器和神经内分泌系统之间的相互作用，并开始表征计时行为背后的细胞和分子信号原理。这里主要关注的是多肽和类固醇激素信号之间的相互作用及其昼夜节律控制。我们的目标也是找出大脑中昼夜节律和发育信号在哪里整合，以确定特定行为的时间。这种特定行为将是果蝇的羽化。果蝇似乎是一个非常适合这个项目的模型系统，因为它在基因和实验上都很容易驯化，并且拥有相对较少的可单独识别的神经元。从长远来看，这为从分子水平到系统水平完整地破译中枢和外周生物钟与靶组织之间的神经元和激素联系提供了可能性。羽化是非常适合的，因为它是由发育和昼夜节律计时器决定的，它的计时受肽和类固醇激素的控制。从动物学的角度来看，了解神经-内分泌网络计时羽化的结构是非常有意义的，因为正确的羽化计时对昆虫和其他节肢动物的生存和健康至关重要，这些节肢动物代表了地球上的绝大多数动物。

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.