The proposed research will examine the mechanisms by which the axonal microtubule array is elaborated during axon extension. The ability of neurons to extend axons over long distances is dependent upon the elaboration of highly organized arrays of microtubules. In the proposed experiments, the role of microtublule transport during axon growth will be addressed in living cells. There are 3 specific aims: (1) In the first aim, microtubule behaviors at the neuronal centrosome will be observed within living neurons to determine whether centrosomal microtubules actually detach and move into the axon. (2) In the second aim, fluorescent tubulin will be introduced into neurons in the form of stable microtubule fragments, assembly-incompetent tubulin subunits, or potential intermediate tubulin aggregates, and it will be determined whether tubulin in any of these forms is actively transported down the axon. (3) In the third aim, microtubule behaviors in the axon that underlie the formation of collateral branches will be investigated. Direct observation as well as pharmacologic tools will be used to determine whether microtubules arise within newly-forming branches via transport from the parent axon. Collectively, these efforts will resolve the contribution of microtubule transport to critical features of axon growth.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
3R01NS034270-02S1
Application #
2767238
Study Section
Neurology B Subcommittee 2 (NEUB)
Program Officer
Leblanc, Gabrielle G
Project Start
1996-09-05
Project End
2000-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Dent, Erik W; Tang, Fangjun; Kalil, Katherine (2003) Axon guidance by growth cones and branches: common cytoskeletal and signaling mechanisms. Neuroscientist 9:343-53
Dent, E W; Kalil, K (2001) Axon branching requires interactions between dynamic microtubules and actin filaments. J Neurosci 21:9757-69
Kalil, K; Szebenyi, G; Dent, E W (2000) Common mechanisms underlying growth cone guidance and axon branching. J Neurobiol 44:145-58
Dent, E W; Callaway, J L; Szebenyi, G et al. (1999) Reorganization and movement of microtubules in axonal growth cones and developing interstitial branches. J Neurosci 19:8894-908
Ferhat, L; Kuriyama, R; Lyons, G E et al. (1998) Expression of the mitotic motor protein CHO1/MKLP1 in postmitotic neurons. Eur J Neurosci 10:1383-93
Yu, W; Sharp, D J; Kuriyama, R et al. (1997) Inhibition of a mitotic motor compromises the formation of dendrite-like processes from neuroblastoma cells. J Cell Biol 136:659-68