Experiments in the current project contribute to an understanding of how precise connections develop between neurons and their targets. Experimental and descriptive studies of a simple vertebrate system, the motor innervation of the chick embryo hindlimb, have shown that selective pathfinding by the growing tips of individual neurites (the """"""""growth cones"""""""") plays a large role in the genesis of precise and orderly connections. The growth cones use navigational cues of two classes during their outgrowth. The first of these are highly specific cues that growth cone use to select the correct pathways at points where pathways diverge. The second set of cues delineate the pathways themselves. Experiments in this project are designed to characterize the spatial extent, source, and development of these axonal guidance cues, using nerve tracing techniques, simple ablation surgeries, and transplants between quail and chick embryos in which the donor tissues can be identified histologically. An important part of the projected study is to analyze the applicability of chimaeric operations between chick and quail to studies is to analyze the aplicability of chimaeric operations between chick and quail to studies of the nervous system. Preliminary results suggest that the chimaeric technique will be invaluable in studying the relationship between tissues in the embryonic environment and the navigation of growth cones. The specific objectives for the next year are to: (1) conclude experiments to determine if the quail/chick chimaeric surgical technique can be used in this system to study growth cone interactions with their environment. (2) conclude the mapping of quail motoneuron pools to determine what differences in axonal projection patterns in quail must be taken into account in analyzing chimaeras. (3) conclude experiments that assess whether navigational cues are provided by tissues between the spinal cord and the limb base. (4) begin embryonic surgeries designed to characterize the distal extent of specific cues that allow axons to choose between dorsal and ventral pathways at the limb base. Analysis of the navigational cues that are effective in specific neuronal pathfinding in the chick hindlimb system should give insights into the normal and abnormal development of the human nervous system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021308-02
Application #
3402299
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1985-04-01
Project End
1988-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
2
Fiscal Year
1986
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
Steketee, Michael B; Tosney, Kathryn W (2002) Three functionally distinct adhesions in filopodia: shaft adhesions control lamellar extension. J Neurosci 22:8071-83
Steketee, M; Balazovich, K; Tosney, K W (2001) Filopodial initiation and a novel filament-organizing center, the focal ring. Mol Biol Cell 12:2378-95
Polinsky, M; Balazovich, K; Tosney, K W (2000) Identification of an invariant response: stable contact with schwann cells induces veil extension in sensory growth cones. J Neurosci 20:1044-55
Steketee, M B; Tosney, K W (1999) Contact with isolated sclerotome cells steers sensory growth cones by altering distinct elements of extension. J Neurosci 19:3495-506
Oakley, R A; Lasky, C J; Erickson, C A et al. (1994) Glycoconjugates mark a transient barrier to neural crest migration in the chicken embryo. Development 120:103-14
Tosney, K W; Dehnbostel, D B; Erickson, C A (1994) Neural crest cells prefer the myotome's basal lamina over the sclerotome as a substratum. Dev Biol 163:389-406
Oakley, R A; Tosney, K W (1993) Contact-mediated mechanisms of motor axon segmentation. J Neurosci 13:3773-92
Erickson, C A; Duong, T D; Tosney, K W (1992) Descriptive and experimental analysis of the dispersion of neural crest cells along the dorsolateral path and their entry into ectoderm in the chick embryo. Dev Biol 151:251-72
Oakley, R A; Tosney, K W (1991) Peanut agglutinin and chondroitin-6-sulfate are molecular markers for tissues that act as barriers to axon advance in the avian embryo. Dev Biol 147:187-206
Tosney, K W (1991) Cells and cell-interactions that guide motor axons in the developing chick embryo. Bioessays 13:17-23

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