Disentangling Self-Avoidance

解除自我回避

• 批准号: 10727641
• 负责人: Wesley B Grueber
• 金额: $ 16.45万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10727641
• 关键词: Affinity; Animals; Axon; Biological Assay; Brain; Brain Diseases; Cell surface; Cells; Complex; Dedications; Dendrites; Development; Disease; Down Syndrome Cell Adhesion Molecule; Drosophila genus; ECM receptor; Ensure; Environment; Extracellular Matrix; Future; Genes; Goals; Integrins; Maintenance; Mediating; Mediator; Membrane; Methods; Molecular; Morphogenesis; Morphology; Nervous System; Nervous System Physiology; Neurofibrillary Tangles; Neurons; Pathway interactions; Phenotype; Process; Research; Resolution; Sampling; Sensory; Structure; Study models; Substrate Interaction; Surface; Synapses; System; Techniques; Work; course development; extracellular; insight; mutant; neuronal circuitry; overexpression; prevent; receptive field; response; somatosensory

SUMMARY Dendrites are the fine, and often highly branched, processes through which neurons receive information from their environment. The morphologies of dendrites are important for connectivity and healthy functioning of the nervous system. Thus, it is critical to understand the genes that control dendrite morphogenesis and maintenance. One key broadly conserved feature of dendrite and axon morphology is their even spreading across territories without overlap. Repulsion between arbors of the same cell, termed self-avoidance, is under the control of two major pathways in Drosophila somatosensory neurons, a powerful model for studies of dendrite morphogenesis. One pathway supports dendrite-dendrite recognition and repulsion and is mediated by Down syndrome cell adhesion molecule 1 (Dscam1). In the absence of this pathway, dendrites cross each other and become tangled, leaving parts of their receptive field uncovered and other parts over-innervated. Another pathway that impacts whether dendritic membranes are available for contact and recognition is mediated by integrin receptors for the extracellular matrix. In the absence of this pathway, dendrite-substrate interactions predominate and dendrites become enclosed by membranes of nearby cells. It is important to discriminate between these two pathways so that the molecular basis for dendrite development can be better understood. However, we still have relatively few insights into how different genes impact these two pathways, so both dendrite-dendrite and dendrites-substrate interactions are not well known. As a result, the potential for these studies to inform our understanding of more complex mammalian systems has not been fully realized. We will use a simple but powerful technique for assaying dendrite-substrate interactions to build a clearer understanding of self-avoidance pathways. We expect that the insights gained can inform us about the development of more complex brains that are more similar to own.

概括 树突是神经元从中接收信息的良好，通常是分支高度分支的过程 他们的环境。树突的形态对于连通性和健康功能很重要 神经系统。因此，了解控制树突形态发生和 维护。树突和轴突形态的一个主要保守特征是它们的传播 在没有重叠的领土上。同一细胞的乔木之间的排斥称为自我避免，在 控制果蝇体感神经元的两种主要途径，这是研究的强大模型 树突形态发生。一条途径支持树突树突识别和排斥，并被介导 由唐氏综合征细胞粘附分子1（DSCAM1）。在没有此途径的情况下，树突越过每个途径 其他并变得纠结，使他们的接受场的一部分被发现，其他部分过度发挥作用。 另一个影响树突状膜是否可以接触和识别的途径是 由整联蛋白受体介导的细胞外基质。在没有此途径的情况下，树突底物 相互作用占主导地位，树突被附近细胞的膜包围。重要的是 区分这两种途径，以使树突发展的分子基础可以更好 理解。但是，我们仍然对不同基因如何影响这两种途径，相对较少的见解， 因此，尚不清楚树突状树突和树突底物相互作用。结果， 这些研究以了解我们对更复杂的哺乳动物系统的理解尚未完全实现。 我们将使用一种简单但功能强大的技术来分析树突 - 底物互动以构建更清晰的 了解自我避免途径。我们希望获得的见解可以告知我们 开发更复杂的大脑，这些大脑与拥有更相似。