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Journal of Neuroscience, Vol 15, 4970-4981, Copyright © 1995 by Society for Neuroscience
Axonal growth and fasciculation linked to differential expression of BDNF and NT3 receptors in developing cerebellar granule cells
RA Segal, SL Pomeroy and CD Stiles
Department of Cell and Molecular Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
In the developing cerebellum, young granule neurons in the external
germinal layer respond preferentially to BDNF, while mature neurons within
the inner portion of the cerebellum respond preferentially to NT3. Here we
show that this anatomic distinction reflects a developmentally regulated
switch at the level of neurotrophin receptor gene expression. The salient
feature of the developmental switch is a change in the ration of mRNA
transcripts encoding functional BDNF and NT3 receptor tyrosine kinases. The
ratio of the BDNF receptor trkB to the NT3 receptor trkC reverses from 5:1
in neonatal cerebellum to 1:3 in adult cerebellum. TrkB and TrkC are
closely related transmembrane tyrosine protein kinases. However, activation
of BDNF and NT3 receptors in cerebellar granule neurons do not give
equivalent biological responses. In aggregate cell culture and single cell
assays, BDNF enhances axonal outgrowth of early granule cells by
influencing neurite elongation. In contrast, NT3 alters the morphology of
outgrowth. Collectively, these findings suggest that regulation of
neurotrophin receptors during cerebellar development is important for the
timing and morphology of axonal growth.
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