I propose to continue my studies of the mechanisms within the axon that are involved in the formation of newly regenerating daughter axons. We will focus specifically on those processes of axonal growth that are relatively independent of changes in transcription and translation in the neuron cell body. The cytoskeleton of a newly regenerated axon is apparently derived from the cytoskeleton of its parent axon. These cytoskeletal elements, which are provided exclusively by slow axonal transport, accumulate at the cut end of the axon. We have proposed that the cytoskeleton is reorganized in this region of the axon and that it is then transported into the regenerating daughter axon. In order to study this process, we have developed a new method for studying the transport of the cytoskeleton from the parent axon into the daughter regenerate. In this method, the cytoskeletal proteins of rat motor axons are selectively labeled by slow axonal transport. This method will be employed to compare the composition and dynamics of the cytoskeleton in parent axons and daughter axons. The goal of these studies is to elucidate the local mechanisms that are involved in the transformation of the axonal cytoskeleton during regeneration. Another aspect of these studies on the basic mechanisms of axonal elongation concerns the translocation of the cytoskeleton through the axon. The squid giant axon will be the primary model used to test the hypothesis that actin and myosin are involved in the mechanisms of cytoskeletal translocation within the axon.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021669-05
Application #
3403035
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1985-04-01
Project End
1991-03-31
Budget Start
1989-04-01
Budget End
1991-03-31
Support Year
5
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106