The long term goal of this research project is to understand how neuronal growth cones reach their correct target sites in the vertebrate central nervous system (CNS). This is a fundamental problem in neuroscience. The delineation of how this is done normally should be important for understanding what goes wrong during developmental diseases of the nervous system and why regeneration following injury to the CNS is normally so poor. Evidence, from research funded by a grant to which this proposal is a continuation demonstrated that: 1) the early spinal cord of fish embryos is extremely simple consisting of a small number of identified neurons and non-neuronal cells; 2) growth cones of the five earliest neuronal classes reach their destinations in the CNS by following stereotyped, cell-specific pathways; 3) the behaviors of identified growth cones at specific sties suggest that identified cells may attract, inhibit, and direct their cell- specific turns. This proposal will test a number of hypotheses generated by this and other studies by laser ablating specific cells in the fish embryonic cord and assaying their effect by a combination of methods. This includes labeling single cells by intracellular dye injections, labeling all neurons or a specific subset of neurons with monoclonal antibodies, and electron microscopy. 1) Do growth cones receive directional cues from specific cells in their environment? 2) Do growth cones become sensitive to certain environmental cues only after interactions with other cells? 3) Can some cells specifically attract certain growth cones? 4) Can some cells specifically inhibit certain growth cones?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS024848-04
Application #
3409800
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1987-04-01
Project End
1993-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Arts and Sciences
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Chandrasekhar, A; Schauerte, H E; Haffter, P et al. (1999) The zebrafish detour gene is essential for cranial but not spinal motor neuron induction. Development 126:2727-37
Yee, C S; Chandrasekhar, A; Halloran, M C et al. (1999) Molecular cloning, expression, and activity of zebrafish semaphorin Z1a. Brain Res Bull 48:581-93
Chandrasekhar, A; Warren Jr, J T; Takahashi, K et al. (1998) Role of sonic hedgehog in branchiomotor neuron induction in zebrafish. Mech Dev 76:101-15
Shoji, W; Yee, C S; Kuwada, J Y (1998) Zebrafish semaphorin Z1a collapses specific growth cones and alters their pathway in vivo. Development 125:1275-83
Chandrasekhar, A; Moens, C B; Warren Jr, J T et al. (1997) Development of branchiomotor neurons in zebrafish. Development 124:2633-44
Kanki, J P; Chang, S; Kuwada, J Y (1994) The molecular cloning and characterization of potential chick DM-GRASP homologs in zebrafish and mouse. J Neurobiol 25:831-45
Kuwada, J Y (1993) Pathway selection by growth cones in the zebrafish central nervous system. Perspect Dev Neurobiol 1:195-203
Bernhardt, R R; Patel, C K; Wilson, S W et al. (1992) Axonal trajectories and distribution of GABAergic spinal neurons in wildtype and mutant zebrafish lacking floor plate cells. J Comp Neurol 326:263-72
Bernhardt, R R; Nguyen, N; Kuwada, J Y (1992) Growth cone guidance by floor plate cells in the spinal cord of zebrafish embryos. Neuron 8:869-82
Chitnis, A B; Patel, C K; Kim, S et al. (1992) A specific brain tract guides follower growth cones in two regions of the zebrafish brain. J Neurobiol 23:845-54

Showing the most recent 10 out of 18 publications