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During development motile growth cones at the tips of growing axons are guided to their targets by environmental cues.
In decision regions where growth cones change direction or branch they often pause for extended time periods and become
large and complex. Some of the extracellular cues that regulate directed advance of the growth cone have been identified but
many of their intracellular signaling pathways are incompletely understood. Ultimately extracellular cues must be transduced
through the actin and microtubule cytoskeleton in the growth cone to cause changes in morphology, motility and forward advance.
High resolution live cell imaging has provided remarkable insight into the dynamic reorganization in the cytoskeleton required
for growth cone behaviors. Biochemical, molecular and genetic studies have identified proteins and other signaling intermediates
that regulate cytoskeletal dynamics.
However, in order to gain a better understanding of axon guidance mechanisms it will be necessary to elucidate how reorganization of the cytoskeleton is regulated in motile growth cones responding to physiological guidance cues. This will require simultaneous visualization of dynamic cytoskeletal changes with temporal and spatial changes in intracellular regulatory signals. Our long term goal is to understand the mechanisms that regulate growth cone guidance and axon branching. We are using a combination of high resolution dynamic imaging with cellular and molecular techniques on both dissociated neurons and slice preparations from the developing mammalian cerebral cortex to investigate how guidance molecules, actin regulatory proteins and calcium signaling events influence behaviors of cortical growth cones through reorganization of the cytoskeleton.