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.

项目摘要 轴突和树突的靶向对于神经系统的正确连接和表达 行为。为了了解神经系统在发育过程中是如何连接的，我们关注细胞-细胞 在连接躯体感觉系统的特殊性基础上的相互作用。躯体感觉很重要 感知触摸和有害刺激，并驱动不同和适当的行为反应。我们专注于 局部轴突-轴突相互作用对回路组织、功能和行为的影响。体感 果蝇系统是探索神经回路连接的细胞和分子基础的良好模型 和功能。在这里，我们关注的是确保强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。 许多正在研究的发育过程，包括轴突-轴突粘连、排斥、细化、轴突 靶标选择，以及通过分子线索和神经活动控制这些过程，是 其他物种的神经系统发育。我们发现，躯体感觉轴突的位置很高 在果蝇的中枢神经系统中订购。这种精确的排序似乎确保了不同的 感觉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。我们认为，发育中的轴突负责感知不同的通道 相互作用，确保分离连接和不同的行为，以响应感觉刺激。 相反，我们提出，相同模式的轴突可能参与积极的吸引人的相互作用 确保接线过程中的凝聚力。我们的目标是测试使正常的健壮的 以及感觉输入和运动输出之间的不同关系。我们建议，至少有一部分 其机制在于不同感觉形式之间的发育轴突-轴突相互作用的层次 而理解这种有序连接是如何出现的，将为我们提供对 神经系统的图案化更普遍，以及图案化在发育过程中可能如何被破坏 神经系统的紊乱。