"This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."
Guidance and targeting of neuronal axons from eye to brain is orchestrated through a set of cues that are being discovered. This project addresses the mechanism by which L1, a key neural cell adhesion molecule, regulates the map of retinal axons to the superior colliculus, a region of the brain that contains a topographic map of the visual world. The function of this system is to direct behavioral responses toward points in surrounding space through eye, head, and arm movements. The hypothesis to be tested is that L1 guides retinal axons to correct synaptic targets by regulating adhesion to a substrate-bound molecule, termed ALCAM, in conjuction with graded axon guidance cues ephrinB and EphB receptors. The role of L1 interactions in synaptic targeting will be studied using a novel L1 mutant mouse that lacks the ability to stabilize adhesion, and mice with genetic deletions in ALCAM and EphB genes. Axon tracing, cell adhesion and axon growth assays using retinal cells from each strain of mice will determine if L1 binds to ALCAM thus promoting ephrinB1-dependent synaptic targeting of retinal axons to proper coordinates in the brain. This project will enhance economic growth and recovery and provide exceptional educational value by scientific training of undergraduates, graduate, and postdoctoral students, and hiring of a research technician. The importance of this work is that it provides the first molecular explanation for how neurons develop reversible anchorage to form an eye-to-brain map.
