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GAP-43 Is Critical for Normal Development of the Serotonergic Innervation in Forebrain

Summary: GAP-43 Is Critical for Normal Development of the Serotonergic
Innervation in Forebrain
Stacy L. Donovan,1 Laura A. Mamounas,3,4 Anne M. Andrews,5 Mary E. Blue,2,3,6 and James S. McCasland1
1Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, New
York 13210, 2Departments of Neurology and 3Neuroscience and 4Division of Neuropathology, Johns Hopkins University
School of Medicine, Baltimore, Maryland 21205, 5Department of Chemistry, The Pennsylvania State University, University
Park, Pennsylvania 16802, and 6Kennedy Krieger Research Institute, Baltimore, Maryland 21205
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 hippocam-
pus in GAP-43­null (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


Source: Andrews, Anne M. - Huck Institutes of the Life Sciences, Pennsylvania State University


Collections: Biology and Medicine