Ph.D. Univ. of California, San Diego, 1971

Axon growth and branching during development and regeneration Many kinds of neurons grow and differentiate well in tissue culture, elaborating axons and dendrites and forming synapses on target cells. We use cultured neurons of various types to examine ways in which axon growth and branching may be controlled during development and regeneration.We re examining the characteristics of motor and sensory axon growth and branching of chick, mouse, and rat neurons. Cultured neurons treated in a variety of ways to interfere with normal signaling pathways reveal alterations in axonal and dendritic arborization patterns. We are especially interested in the use of botulinum toxin (type A) to better understand mechanisms that regulate axon branching. Botulinum A toxin is a neurotoxin that blocks synaptic vesicle release and concomitantly causes pronounced axon branching in vivo and in vitro. Human patients suffering various spasmodic muscle disorders such as blepharospasm can be treated with toxin for relief of symptoms but motor axon branching and growth of sprouts to muscle fibers results in formation of new synapses and the eventual return of symptoms.We hope to be able to better understand signaling pathways involved in modulating axon growth, branch formation, and regeneration.