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）：我研究的长期目标是了解细胞间通讯的细胞和分子机制，这些机制影响神经肌肉发育，包括功能性突触的形成。具体来说，我们将解决神经胶质细胞的相互作用，影响果蝇发育中的成年神经支配的重塑的性质。我们使用果蝇（成年）背纵（飞行）肌的运动系统作为模型。成体神经支配在变态期间发育，这是一个以包括神经系统在内的许多组织的广泛重塑为特征的阶段。我们已经表明，运动神经元制定过多的二阶分支，这一时期之后是一个修剪阶段，在此期间，几乎70%的分支被消除。结果，建立了DLM神经支配的成人模式。这项建议的重点是在其中一个小的运动神经元分支的子集是稳定的修剪阶段生存的方式，并测试在稳定的过程中的胶质细胞的作用。提出了三个主要目标：1）在神经支配发育的背景下检查胶质细胞的分化; 2）通过操纵它们的发育来测试胶质细胞在稳定中的作用。3)研究细胞粘附分子Fasll在神经胶质细胞相互作用中的作用。大多数关于果蝇神经肌肉发育的研究都集中在幼虫阶段的发育可塑性上，而成年对应物的发育仍有待于同样详细的探索。我们对运动轴突稳定性的研究至少有四个目的：i）在三方突触的背景下研究神经肌肉系统的发育，这不仅包括突触前和突触后的伙伴，而且还包括第三个重要的细胞，胶质细胞; ii）研究胶质细胞的作用，（在轴突分支的保护），尚未在果蝇中报道; iii）在果蝇中DLM神经支配的重塑期间明显的发育可塑性要深刻得多，并且与在脊椎动物神经系统发育期间观察到的轴突修剪具有惊人的相似性。此外，已知神经胶质在脊椎动物神经肌肉发育期间具有保护作用;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，其涉及人类病症，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。