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Journal of Neuroscience, Vol 16, 1740-1752, Copyright © 1996 by Society for Neuroscience
Expression of TrkB receptor isoforms in the developing avian visual system
AS Garner, HJ Menegay, KL Boeshore, XY Xie, JM Voci, JE Johnson and TH Large
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4975, USA.
The expression of novel TrkB receptor transcripts has been characterized to
understand the potentially diverse roles of brain- derived neurotrophic
factor (BDNF) in the developing avian visual system. In situ localization
with an extracellular domain probe common to all TrkB transcripts labeled a
sub-population of large retinal ganglion cells as well as many associated
visual nuclei, including the neuronal layers within the tectum that receive
retinal innervation. Because of the potential for structurally and
functionally distinct receptors derived from the TrkB gene locus, cDNA
cloning and reverse transcription-PCR analysis were used to further analyze
receptor isoform expression in the retina and tectum. Receptor isoforms
were sequenced that contained a deletion of the N terminus, a deletion in
the putative ligand-binding domain, or a deletion in the cytoplasmic
juxtamembrane (JM) domain. Two novel JM insertion sequences also were
identified, one of which exhibits weak homology to beta-actin and was found
in both kinase-containing (TK+) and kinase deletion (KD) receptor isoforms.
In the developing retina, TK+ receptor mRNA is upregulated during the
period of retinal ganglion cell (RGC) death, consistent with the proposed
role of BDNF as a tectal-derived survival factor for RGCs. However, the
expression of TK+ transcripts in the tectum indicates that this structure
also contains cells responsive to BDNF throughout development. Because BDNF
is expressed in both the retina and tectum, it is conceivable that TrkB
also mediates autocrine/paracrine signaling within these structures or
anterograde retinotectal trophic support.
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