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

Miami University Oxford, Oxford OH

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Abstract

[unreadable] 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. [unreadable] [unreadable]