The long term objective of this research proposal is to understand how cerebellar granule neurons induce dendritic differentiation of Purkinje cells. The experiments described here use a novel culture system comprised of purified murine granule and Purkinje cells, alone or together in vitro. This purified, in vitro approach eliminates the confounding influence of many other cell types that have been present in previous in work. The defined cell culture system allows testing of various agents for effects specifically on the Purkinje cell. One set of proposed experiments constitutes a physical/biochemical approach that makes no assumptions a priori about the nature of the granule neuron signal for Purkinje cell differentiation. A second set of experiments represents the """"""""candidate gene"""""""" approach, in which neurotrophins, growth factors, or depolarizing agents previously suggested to affect neuronal development are tested for their expression and effects during granule neuron-induced Purkinje cell differentiation. These studies will identify cues that trigger cerebellar neuronal development, and may reveal new agents with therapeutic value in treating neurodegenerative diseases of the cerebellum.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
2F32NS009864-03
Application #
2522678
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1998-03-01
Project End
Budget Start
1997-09-12
Budget End
1998-09-11
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Pathology
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Mason, C A; Morrison, M E; Ward, M S et al. (1997) Axon-target interactions in the developing cerebellum. Perspect Dev Neurobiol 5:69-82