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Content archived on 2024-06-18

The molecular mechanisms of axon re-extension following developmental axon pruning

Objective

Lack of neuronal regeneration following injury such as spinal cord injury is the major cause for poor functional recovery. It has long been appreciated that young neurons can grow, undergo reorganization and synapse on appropriate targets during development while adult neurons cannot, however the molecular basis of these differences remain unclear. Studying the molecular mechanisms that regulate axon re-extension following remodeling during development holds the promise to uncover molecular rules underlying this phenomena and are therefore of great potential. A model system that allows a unique molecular exploration of axon re-extension is that of axon pruning in Drosophila. Pruning is a process in which neurons first extend excessive branches, later prune away inappropriate ones with precise spatial and temporal control and, at least in the some cases, re-extend their axons to form mature connections. Pruning was found to essential for sculpting the mature nervous systems of vertebrates and invertebrates. During my post-doctoral studies, I performed a mosaic screen and identified a mutant exhibiting normal pruning but lacking the stereotypical axon re-extension that follows. Remarkably, other neurons, belonging to the mutant clone but which do not undergo pruning, extend their axons normally at the same developmental time, indicating that the mutation selectively affected axon re-extension following pruning but not axon extension per se. This novel finding suggests that there is molecular switch dedicated to changing the growing status of a neuron. The causal gene was mapped to an uncharacterized steroid hormone receptor, HR51. Here, I propose to characterize the role of HR51 in axon re-extension as well as identify its ligand. In addition I propose to perform a suppressor screen directed at identifying additional molecules involved in axon re-extension. Taken together, these three aims should provide insight into the molecular mechanisms of axon re-extension.

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Topic(s)

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Call for proposal

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FP7-PEOPLE-IRG-2008
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Funding Scheme

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MC-IRG - International Re-integration Grants (IRG)

Coordinator

WEIZMANN INSTITUTE OF SCIENCE
EU contribution
€ 100 000,00
Address
HERZL STREET 234
7610001 Rehovot
Israel

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Activity type
Higher or Secondary Education Establishments
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Total cost

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