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Journal of Neuroscience, Vol 15, 2888-2905, Copyright © 1995 by Society for Neuroscience
Regulation of TrkA and ChAT expression in developing rat basal forebrain: evidence that both exogenous and endogenous NGF regulate differentiation of cholinergic neurons
Y Li, DM Holtzman, LF Kromer, DR Kaplan, J Chua-Couzens, DO Clary, B Knusel and WC Mobley
Department of Neurology, University of California at San Francisco 94143, USA.
TrkA is a receptor tyrosine kinase whose activation transduces NGF
signaling. TrkA expression has been demonstrated in NGF-responsive adult
basal forebrain cholinergic neurons (BFCNs). Several lines of evidence have
suggested that endogenous NGF plays a role in the development and
differentiation of these neurons. We examined TrkA expression during
development. TrkA mRNA and protein were present in basal forebrain neurons
during the entire postnatal period; the distribution of neurons bearing
these markers was identical to that for those containing choline
acetyltransferase (ChAT) mRNA, suggesting that, as in the adult, TrkA gene
expression is localized to BFCNs. The expression of TrkA and ChAT followed
a very similar temporal pattern, suggesting regulation by the same
factor(s). We discovered that NGF administration in vivo activated TrkA
receptors, and increased both TrkA and ChAT mRNA; conversely, anti-NGF
infusions suppressed expression of both genes. These results suggest that
endogenous NGF regulates expression of TrkA and ChAT. Finally, while NGF
infusion increased the size of developing BFCNs, NGF antibodies inhibited
the normal developmental increase. The results are evidence that endogenous
NGF acts on developing BFCNs to enhance gene expression and cellular
differentiation.
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