The role of Hox genes in the specification of circuits controlling specialised behaviours

动物，无论是老鼠、苍蝇还是人类，都会沿着它们的身体轴线产生与不同的专门身体部位相关的不同刻板印象的动作。例如，我们呼吸(横隔膜)、咀嚼(下巴)和走路(腿)。控制这些运动的神经回路位于神经系统轴线上的不同位置。这意味着，随着神经系统的发育，位于不同位置的神经细胞组被专门组装起来，为这些特殊的行为制造不同的回路。这是如何控制的？我们知道HOX基因在这一过程中发挥了作用，我的实验旨在确切地展示这些基因如何控制运动所需的局部特定神经细胞模式的形成。我将使用果蝇，因为不同动物之间的发育机制是保守的，而且果蝇在遗传和细胞操作方面非常优秀。果蝇的另一个优点是，神经系统的不同部分是由沿着前后轴重复的相似的祖细胞集组成的。所以我要问的问题是，Hox基因如何控制这些相同的细胞组组装成不同的专门网络，以适应特定的运动模式？尽管这项工作的目的是揭示基本原理，但它有可能造福社会。人类神经系统的许多疾病(如精神分裂症、癫痫和自闭症)很可能是由发育早期神经网络的不正确组装引起的。通过研究果蝇神经发育的机制，我们可以揭示核心原理，这些原理随后可以用于指导旨在了解人类神经疾病发育基础的临床研究。

Animals, mouse, fly or humans, generate different stereotyped movements associated with different specialized body parts along their body axes. We, for example breathe (diaphragm), chew (jaws) and walk (legs). The nerve circuits that control these movements are located at different points along the axis of the nervous system. This means that, somehow, as the nervous system develops, groups of nerve cells at different positions are specifically assembled to make the different circuits for these specialised behaviours. How is this controlled? We know that the Hox genes have a role in this process and my experiments are designed to show exactly how these genes control the formation of locally specific patterns of nerve cells required for movement. I will use the fruitfly Drosophila because developmental mechanisms are conserved between different animals and because Drosophila is excellent for genetic and cellular manipulations. Another advantage of the fruitfly is that the different parts of the nervous system arise from similar sets of progenitor cells that are repeated along the anterioposterior axis. So the question I will ask is How Hox genes control the assembly of these of equivalent sets of cells into different specialized networks for specific patterns of movement?Although the work is aimed at uncovering fundamental principles it has potential to benefit society. It is likely that many diseases of the human nervous system (e.g. schizophrenia, epilepsy and autism) arise from the improper assembly of neural networks early in development. By studying the mechanisms of neural development in flies, we can uncover core principles that could subsequently be used to inform clinical research aimed at understanding the developmental basis of human neural disorders.