Engrailed and the control of synaptic circuits in adult Drosophila

摘要 增强型(EN)是一种转录因子；一种与DNA结合并开启或关闭其他基因的蛋白质。它 最初在果蝇中发现，但后来发现在所有动物中都存在，在动物中发挥着重要作用 在控制神经元或神经细胞的发育方面。这项研究的长期目标是找出 EN控制大脑内神经细胞相互连接(形成突触)的方式，具有特定的 专注于识别和表征它所调控的基因和分子网络。这项建议 使用果蝇听觉神经元到巨细胞纤维(GF)突触作为模型系统， 研究EN在控制突触连接中的作用。第一个具体目标将是使用 电生理学和解剖染色技术测量听神经元动作电位和 随着动物年龄的增长，输出突触到GF的变化，并确定是否存在性别特异性 不同之处。第二个具体目标将是研究改变EN存在的量的影响 成年动物的神经元。与哺乳动物神经元一样，en在果蝇听神经元中持续表达 但其在这一时期的功能尚不清楚。它或许可以保持他们的 电学特性或它们突触连接的模式。为了测试这一点，将使用遗传方法来 在不同的时间加入或去除感觉神经元中的EN。 这项研究与公共健康有关，因为人类EN与几种大脑疾病有关，例如 帕金森氏症和自闭症。果蝇模型对于分子的发现特别有用 与人类直接相关的途径，因为这些途径中的大多数在 进化论。所有的动物都有EN蛋白，所以很可能任何受EN蛋白调控的分子 果蝇的突触形成过程与人类类似，在脑中扮演着类似的角色 发展。

Abstract Engrailed (En) is a transcription factor; a protein that binds to DNA and that switches on or off other genes. It was first discovered in Drosophila but later found to be present in all animals, where it plays an important role in controlling the development of neurons, or nerve cells. The long-term goal of this research is to find out how En controls the way that nerve cells connect to each other (form synapses) within the brain, with a particular focus on identifying and characterizing the network of genes and molecules that it regulates. This proposal uses the Drosophila auditory neuron – to – giant fiber (GF) synapse as a model system with which to investigate the role of En in the control of synaptic connections. The first specific aim will be to use electrophysiology and anatomical staining techniques to measure how auditory neuron action potentials and output synapses to the GF change as the animal ages, and to determine whether there are sex-specific differences. The second specific aim will be to study the effects of changing the amounts of En present in the neurons in the adult animal. As in mammalian neurons, En expression in Drosophila auditory neurons persists through adult life, but its functions during this period are not understood. It could perhaps maintain their electrical properties or the patterns of their synaptic connections. To test this, genetic methods will be used to add or take away En from the sensory neurons at different times. This work is relevant to public health because human En has been linked to several brain disorders, such as Parkinson’s disease and autism. Drosophila models are particularly useful for the discovery of molecular pathways that are directly relevant to humans, because most of these pathways have been conserved during evolution. All animals have En protein, so it is very likely that any molecules that are regulated by it during the process of synapse formation in Drosophila have their counterparts in humans, playing similar roles in brain development.