The proposed research is designed as analytical and manipulative investigations of mechanisms critical to cell migration and nerve fiber outgrowth in patterning of the developing nervous system. The studies will focus on growth factors influencing these events during early stages of neurogenesis, and will examine the potential of these factors to enhance and guide later regenerative growth. The developing trigeminal (V) motor nucleus in the chick embryo will be used as a model system. For these studies, tissue culture techniques will be used to evaluate the role of the trigeminal ganlion and normal target tissue (jaw muscle) in providing trophic or directing effects on fiber outgrowth and somal translocation. Our previous in vivo studies have indicated the ganglion is vital to normal development of V motor nucleus, and our in vivo and in vitro studies suggest that muscle tissue plays a trophic or directing role during later developmental stages. Basal plate explants of the trigeminal region, taken before the onset of cell migration and nerve fiber outgrowth, will be cultured alone, with disaggregated ganglion tissue, with control neural tissue, with ganlia conditioned media, with whole ganglia plated in varying positions, and with appropriate and inappropriate muscle tissue. Explants from embryos at later developmental stages will also be grown alone and with ontogenetically sequenced ganglionic tissue or target musculature in order to examine the potential of these tissues to provide their trophic influences during later stages, and the capacity of the V motoneurons to respond to these influences during their subsequent development. These studies will be significant in analyzing previously unknown growth factors, and the capacity of these factors to direct both initial neurogenesis and later regenerative growth. Such analyses will contribute to an improved understanding of normal nervous system development and may provide insights which will have significance in remediation of nervous system damage.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020387-05
Application #
3400736
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1983-12-01
Project End
1989-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Florida
Department
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Heaton, M B; Swanson, D J; Paiva, M (1993) Neurotrophic activity in embryonic chick brain: early appearance and differential regional distribution. Dev Neurosci 15:1-9
Heaton, M B; Swanson, D J; Paiva, M et al. (1992) Ethanol exposure affects trophic factor activity and responsiveness in chick embryo. Alcohol 9:161-6
Wayne, D B; Heaton, M B (1990) The ontogeny of specific retrograde transport of nerve growth factor by motoneurons of the brainstem and spinal cord. Dev Biol 138:484-98
Heaton, M B; Paiva, M; Swanson, D (1990) Comparative responsiveness of early chick neural tube neurons to muscle-conditioned medium, laminin, NGF and fibronectin. Brain Res Dev Brain Res 52:113-9
Wayne, D B; Heaton, M B (1990) The response of cultured trigeminal and spinal cord motoneurons to nerve growth factor. Dev Biol 138:473-83
Heaton, M B (1989) Comparative responsiveness of early chick embryo brainstem and spinal cord neurons to target-conditioned medium. Dev Neurosci 11:391-6
Heaton, M B (1989) Influence of laminin on the responsiveness of early chick embryo neural tube neurons to nerve growth factor. J Neurosci Res 22:390-6
Wayne, D B; Heaton, M B (1988) Retrograde transport of NGF by early chick embryo spinal cord motoneurons. Dev Biol 127:220-3
Heaton, M B (1988) Species specificity in the responsiveness of chick embryo neural tube explants to target-conditioned medium. Brain Res 466:152-4
Heaton, M B (1988) Some characteristics of muscle-conditioned media with excitatory and inhibitory influences on neurite outgrowth from early neural tube explants. J Neurosci Res 19:57-61

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