Mechanical Force Underlying Neuronal Shape and Growth

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The mammalian nervous system is analogous to an electrical wiring system that sends messages to all parts of the body. The axon is an exceptionally long "electric wire" extension of the neuron and conducts the electrical signals generated in the nervous system. Though it is not fully understood how axons reach their targets, it is known that axons expand as a result of the slow movement of its front end, the growth cone. As the growth cone slowly moves around the body, the axon lengthens from behind. Filamentous proteins of the cytoplasm, actin, microtubules, and intermediated filaments compose a dynamic skeletal structure for cells, that underlies the ability of axons to elongate. This research project will focus on describing the motility of the lammellipodial growth cone. Mechanical tension is expected to regulate the cytoskeleton during axonal elongation. This ideas is supported by thermodynamic considerations that suggest the assemble of filaments is affected by mechanical forces. The relationship between mechanical tension and two other known stimulators of axonal elongation; nerve growth factor and electrical fields will be investigated to determine whether growth signals transduce through tension or act independently. In conjunction with these studies, the Principal investigator will study the assembly of microtubules during the process of axonal initiation and ascertain what chemicals are responsible for the motility of growth cones by using tension measuring methods. These cytomechanical investigations will provide new insight in understanding axonal development in the nervous system.