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

Hox 基因在控制特殊行为的回路规范中的作用

基本信息

批准号：
BB/X009289/1
负责人：
Jimena Berni
金额：
$ 71.43万
依托单位：
University of Sussex
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2023
资助国家：
英国
起止时间：
2023 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FX009289%2F1
关键词：
role Hox genes specification circuits

项目摘要

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.

动物，老鼠，苍蝇或人类，产生不同的刻板动作与不同的专门身体部位沿着他们的身体轴。例如，我们呼吸（隔膜），咀嚼（下巴）和行走（腿）。控制这些运动的神经回路位于沿着神经系统轴的不同点。这意味着，随着神经系统的发育，不同位置的神经细胞群被专门组装，为这些专门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显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，因为发育机制在不同动物之间是保守的，因为果蝇非常适合遗传和细胞操纵。果蝇的另一个优点是神经系统的不同部分来自于相似的祖细胞，这些祖细胞沿着前后轴重复。所以我要问的问题是Hox基因是如何控制这些等价的细胞集合组装成不同的专门网络，以实现特定的运动模式的？虽然这项工作的目的是揭示基本原则，但它有可能造福社会。人类神经系统的许多疾病（例如精神分裂症、癫痫和自闭症）可能是由于神经网络在发育早期组装不当引起的。通过研究果蝇神经发育的机制，我们可以揭示核心原则，这些原则随后可用于指导旨在了解人类神经疾病发育基础的临床研究。