Dendritic patterning by interacting extrinsic cues

通过相互作用的外部线索形成树突图案

• 批准号: 10527168
• 负责人: Wesley B Grueber
• 金额: $ 2.21万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10527168
• 关键词: Adhesions; Automobile Driving; Axon; Behavior; Cell Communication; Cells; Cues; Dendrites; Development; Developmental Process; Drosophila genus; Ensure; Lead; Modality; Modeling; Molecular; Motor output; Nervous system structure; Neuraxis; Pattern; Positioning Attribute; Process; Resolution; Sensory; Specificity; Stimulus; System; Testing; Touch sensation; behavioral response; cohesion; developmental disease; insight; nervous system development; nervous system disorder; neural circuit; relating to nervous system; response; segregation; sensory input; somatosensory

Project Summary The targeting of axons and dendrites is essential for proper wiring of the nervous system and the expression of behavior. To understand how the nervous system is wired during development we focus on cell-cell interactions that underlie specificity in wiring the somatosensory system. Somatosensation is important for sensing touch and noxious stimuli, and for driving distinct and appropriate behavioral responses. We focus on the influence of local axon-axon interactions in circuit organization, function, and behavior. The somatosensory system of Drosophila is an excellent model to probe the cellular and molecular basis for neural circuit wiring and function. Here we focus on the developmental mechanisms that ensure robust axon segregation to different parts of the nervous system and how these patterns ensure appropriate neural circuit functioning. Many of the developmental processes under study, including axon-axon adhesion, repulsion, refinement, axon target selection, and the control of these processes by molecular cues and neural activity, are central to nervous system development in other species. We find that the positioning of somatosensory axons is highly ordered in the Drosophila central nervous system. This precise ordering appears to ensure that different qualities of sensory information are passed to correct downstream circuits and lead to appropriate behavioral responses. We propose that developing axons that are responsible for sensing different modalities engage in interactions that ensure separation of connections and distinct behaviors in response to sensory stimulation. By contrast we propose that axons of the same modality may engage in positive attractive interactions that ensure cohesion during wiring. We aim to test the developmental mechanisms that enforce the normally robust and distinct relationships between sensory input and motor output. We propose that at least part of the mechanism lies in a hierarchy of developmental axon-axon interactions between different sensory modalities and that understanding how this orderly wiring emerges will provide insights into the mechanisms by which nervous systems are patterned more generally, and how patterning might be disrupted in developmental disorders of the nervous system.

项目概要 轴突和树突的靶向对于神经系统的正确连接和表达至关重要 行为。为了了解神经系统在发育过程中如何连接，我们关注细胞与细胞 构成体感系统连接特异性的相互作用。体感对于 感知触摸和有害刺激，并驱动独特且适当的行为反应。我们专注于 局部轴突-轴突相互作用对电路组织、功能和行为的影响。体感 果蝇系统是探索神经回路布线的细胞和分子基础的优秀模型 和功能。在这里，我们重点关注确保稳健的轴突分离的发育机制 神经系统的不同部分以及这些模式如何确保适当的神经回路功能。 正在研究的许多发育过程，包括轴突-轴突粘附、排斥、细化、轴突 目标选择以及通过分子线索和神经活动控制这些过程是核心 其他物种的神经系统发育。我们发现体感轴突的定位高度 果蝇中枢神经系统中的命令。这种精确的排序似乎可以确保不同的 感官信息的质量被传递到正确的下游电路并导致适当的行为 回应。我们建议开发负责感知不同模式的轴突参与 确保响应感官刺激的连接和不同行为的分离的相互作用。 相比之下，我们认为相同模式的轴突可能会参与积极的吸引相互作用， 确保接线时的凝聚力。我们的目标是测试强制正常稳健的发展机制 以及感觉输入和运动输出之间的明显关系。我们建议至少部分 机制在于不同感觉模式之间发育轴突-轴突相互作用的层次结构 了解这种有序布线是如何出现的，将有助于深入了解这种有序布线的机制 神经系统的模式更普遍，以及模式在发育过程中如何被破坏 神经系统疾病。