Studies attempting to define roles for glia and unique molecules that they express during development versus those expressed during trauma would greatly benefit from a model system where these structural elements could be readily related to functional organization. The investigator and associates have recently discovered boundaries of glia and transiently-expressed glycoconjugates during mammalian brain development that predict a characteristic pattern - functional units referred to as barrels that represent individual facial vibrissae in the mouse. The cells and molecules of developmental, pattern formation boundaries are also associated with synaptic boundaries present in the late postnatal and adult brain. Additionally, some of the same glial constituents found in boundaries around developing functional units in the brain are also expressed in the wounded, adult brain. It is now important to characterize and compare specific cellular and molecular constituents of developmental boundaries and glial """"""""scars"""""""", since one is apparently pre-programmed and the other induced following trauma, yet both may function to deter neurite growth. Immunocytochemistry studies of glia and adhesion/extracellular matrix molecules (e.g., J1/tenascin and a possible proteoglycan ligand) will be performed during embryonic and postnatal development of cortical and subcortical vibrissae centers to determine precise times of appearance and disappearance of these important cellular and molecular determinants of development. The early organization, developmental regulation, and lesion-induced reorganization of glia and glycoconjugates in the somatosensory cerebral and cerebellar cortices will be compared with controlled developmental processes using organotypic cultures from normal veruss lesioned animals. If the glial/glycoconjugate boundaries observed during normal brain development possess elements in common with or distinct from those associated with glial scars in the mature brain following trauma or in neurodegenerative disease, one must categorize all of these elements and attempt to alter their expressions in order to facilitate CNS regeneration.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS020856-07
Application #
3401532
Study Section
Neurology A Study Section (NEUA)
Project Start
1984-12-01
Project End
1994-11-30
Budget Start
1990-12-01
Budget End
1991-11-30
Support Year
7
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163
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Thomas, L B; Gates, D J; Richfield, E K et al. (1995) DNA end labeling (TUNEL) in Huntington's disease and other neuropathological conditions. Exp Neurol 133:265-72
Steindler, D A; Settles, D; Erickson, H P et al. (1995) Tenascin knockout mice: barrels, boundary molecules, and glial scars. J Neurosci 15:1971-83
Steindler, D A; Faissner, A; Harrington, K L (1994) A unique mosaic in the visual cortex of the reeler mutant mouse. Cereb Cortex 4:129-37
Steindler, D A (1993) Glial boundaries in the developing nervous system. Annu Rev Neurosci 16:445-70
Brodkey, J A; Gates, M A; Laywell, E D et al. (1993) The complex nature of interactive neuroregeneration-related molecules. Exp Neurol 123:251-70
Gates, M A; O'Brien, T F; Faissner, A et al. (1993) Neuron-glial interactions during the in vivo and in vitro development of the nigrostriatal circuit. J Chem Neuroanat 6:179-89
O'Brien, T F; Faissner, A; Schachner, M et al. (1992) Afferent-boundary interactions in the developing neostriatal mosaic. Brain Res Dev Brain Res 65:259-67
Laywell, E D; Dorries, U; Bartsch, U et al. (1992) Enhanced expression of the developmentally regulated extracellular matrix molecule tenascin following adult brain injury. Proc Natl Acad Sci U S A 89:2634-8

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