@article{Donovan01052002,
author = {Donovan, Stacy L. and Mamounas, Laura A. and Andrews, Anne M. and Blue, Mary E. and McCasland, James S.}, 
title = {GAP-43 Is Critical for Normal Development of the Serotonergic Innervation in Forebrain},
volume = {22}, 
number = {9}, 
pages = {3543-3552}, 
year = {2002}, 
doi = {10.1523/JNEUROSCI.22-09-03543.2002}, 
abstract ={Serotonergic (5-HT) axons from the raphe nuclei are among the earliest afferents to innervate the developing forebrain. The present study examined whether GAP-43, a growth-associated protein expressed on growing 5-HT axons, is necessary for normal 5-HT axonal outgrowth and terminal arborization during the perinatal period. We found a nearly complete failure of 5-HT immunoreactive axons to innervate the cortex and hippocampus in GAP-43–null (GAP43−/−) mice. Abnormal ingrowth of 5-HT axons was apparent on postnatal day 0 (P0); quantitative analysis of P7 brains revealed significant reductions in the density of 5-HT axons in the cortex and hippocampus of GAP43−/− mice relative to wild-type (WT) controls. In contrast, 5-HT axon density was normal in the striatum, septum, and amygdala and dramatically higher than normal in the thalamus of GAP43−/− mice. Concentrations of serotonin and its metabolite, 5-hydroxyindolacetic acid, and norepinephrine were decreased markedly in the anterior and posterior cerebrum but increased in the brainstem of GAP43−/− mice. Cell loss could not account for these abnormalities, because unbiased stereological analysis showed no significant difference in the number of 5-HT dorsal raphe neurons in P7 GAP43−/− versus WT mice. The aberrant 5-HT innervation pattern persisted at P21, indicating a long-term alteration of 5-HT projections to forebrain in the absence of GAP-43. In heterozygotes, the density and morphology of 5-HT axons was intermediate between WT and homozygous GAP43−/− mice. These results suggest that GAP-43 is a key regulator in normal pathfinding and arborization of 5-HT axons during early brain development.}, 
URL = {http://www.jneurosci.org/content/22/9/3543.abstract}, 
eprint = {http://www.jneurosci.org/content/22/9/3543.full.pdf+html}, 
journal = {The Journal of Neuroscience} 
}