Axon stabilization: A role for glia in patterning adult innervation in Drosophila

轴突稳定：胶质细胞在果蝇成体神经支配模式中的作用

• 批准号: 7127858
• 负责人: JOYCE J FERNANDES
• 金额: $ 21.3万
• 依托单位: MIAMI UNIVERSITY OXFORD
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7127858
• 关键词: Drosophilidae; antibody; cell adhesion; cell cell interaction; cell differentiation; confocal scanning microscopy; gene expression; glia; immunocytochemistry; immunofluorescence technique; molecular /cellular imaging; motor neurons; neural transmission; neuromuscular junction; neuronal guidance; synaptogenesis; transcription factor

DESCRIPTION (provided by applicant): The long-term goal of my research is to understand the cellular and molecular mechanisms of cell-cell communication that patterns neuromuscular development, including the formation of functional synapses. Specifically, we will address the nature of neuro-glial interactions that influence remodeling of the developing adult innervation in Drosophila. We use the motor system of the (adult) Dorsal Longitudinal (flight) Muscles of Drosophila as a model. The adult innervation develops during metamorphosis, a phase which is characterized by extensive remodeling of many tissues including the nervous system. We have shown that motor neurons elaborate excessive second order branches, and this period is followed by a phase of pruning during which almost 70% of the branches are eliminated. As a result, the adult pattern of DLM innervation is established. This proposal focuses on the manner in which a small subset of motor neuron branches is stabilized to survive the pruning phase, and tests the role of glia in the process of stabilization. Three main objectives are presented: 1) Examining the differentiation of glia in the context of the developing innervation; 2) Testing the role of glia in stabilization by manipulating their development. 3) Investigating the role of the cell-adhesion molecule, Fasll, in neuro-glial interactions. Most of the studies on neuromuscular development in Drosophila have focused on the developmental plasticity present in the larval stages, and development of the adult counterpart remains to be explored in the same detail. Our studies of motor axon stabilization will serve at least four purposes: i) examine development of the neuromuscular system in the context of a tripartite synapse, that includes not only the pre-and post synaptic partners but also a third important cell, the glia; ii) investigate a role for glia (in protection of axonal branches) that has not yet been reported in Drosophila; iii) The developmental plasticity evident during the remodeling of DLM innervation in Drosophila is much more profound and bears striking similarities to axonal pruning that is observed during vertebrate nervous system development. Additionally, glia are known to have protective roles during vertebrate neuromuscular development; thus our system can be used as a model for a better understanding of vertebrate events; iv) On a broader level, a better understanding neuro- glial interactions, which have been implicated in human conditions such as epilepsy, schizophrenia, cerebral ischemia, multiple sclerosis, as well as neurodegenerative diseases.

描述（由申请人提供）：我的研究的长期目标是了解细胞 - 细胞通信的细胞和分子机制，该通信模式了神经肌肉发育，包括功能突触的形成。具体而言，我们将解决影响果蝇中发展成人神经的重塑的神经胶质相互作用的性质。我们使用果蝇的（成人）背侧纵向（飞行）肌肉的运动系统作为模型。成年神经神经在变形过程中发展，这种阶段的特征是对包括神经系统在内的许多组织进行了广泛的重塑。我们已经表明，运动神经元详细介绍了过度的二阶分支，此期间是修剪阶段，在此期间消除了几乎70％的分支。结果，建立了DLM神经的成年模式。该建议的重点是稳定运动神经元分支的一小部分以生存修剪阶段的方式，并测试了神经胶质在稳定过程中的作用。提出了三个主要目标：1）在发展神经的背景下检查神经胶质的分化； 2）通过操纵其发育来测试神经胶质在稳定中的作用。 3）研究细胞粘附分子FASLL在神经胶质相互作用中的作用。关于果蝇神经肌肉发育的大多数研究都集中在幼虫阶段中存在的发展可塑性上，成人对应物的发展仍有相同的详细信息进行探讨。我们对运动轴突稳定的研究将至少有四个目的：i）在三方突触的背景下检查神经肌肉系统的发展，其中不仅包括突触前和突触后伴侣，还包括第三个重要细胞，神经胶质； ii）研究果蝇中尚未报道的神经胶质的作用（在轴突分支的保护中）； iii）在果蝇中DLM神经重塑过程中，显而易见的可塑性更加深刻，并且与脊椎动物神经系统发育过程中观察到的轴突修剪相似。此外，已知神经胶质在脊椎动物神经肌肉发育过程中具有保护作用。因此，我们的系统可以用作更好地理解脊椎动物事件的模型。 iv）在更广泛的水平上，更好地理解神经胶质相互作用，与人类状况有关，例如癫痫，精神分裂症，脑缺血，多发性硬化症以及神经退行性疾病。