QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (29) Citing Articles via Google Scholar Google Scholar Articles by Donovan, S. L. Articles by McCasland, J. S. Search for Related Content PubMed PubMed Citation Articles by Donovan, S. L. Articles by McCasland, J. S. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH

 Previous Article  |  Next Article 

The Journal of Neuroscience, May 1, 2002, 22(9):3543-3552

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

Stacy L. Donovan¹, Laura A. Mamounas^{3, 4}, Anne M. Andrews⁵, Mary E. Blue^{2, 3, 6}, and James S. McCasland¹

¹ Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, New York 13210, ² Departments of Neurology and ³ Neuroscience and ⁴ Division of Neuropathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, ⁵ Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, and ⁶ Kennedy 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 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.

Key words: serotonin; terminal arborization; neocortex; hippocampus; GAP-43; denervation; knock-out mice

---

Copyright © 2002 Society for Neuroscience  0270-6474/02/2293543-10$05.00/0

This article has been cited by other articles:

				G. Estivill-Torrus, P. Llebrez-Zayas, E. Matas-Rico, L. Santin, C. Pedraza, I. De Diego, I. Del Arco, P. Fernandez-Llebrez, J. Chun, and F. R. De Fonseca Absence of LPA1 Signaling Results in Defective Cortical Development Cereb Cortex, April 1, 2008; 18(4): 938 - 950. [Abstract] [Full Text] [PDF]

				M. J. Albright, M. C. Weston, M. Inan, C. Rosenmund, and M. C. Crair Increased Thalamocortical Synaptic Response and Decreased Layer IV Innervation in GAP-43 Knockout Mice J Neurophysiol, September 1, 2007; 98(3): 1610 - 1625. [Abstract] [Full Text] [PDF]

				S. Alcantara, E. Pozas, C. F. Ibanez, and E. Soriano BDNF-modulated Spatial Organization of Cajal-Retzius and GABAergic Neurons in the Marginal Zone Plays a Role in the Development of Cortical Organization Cereb Cortex, April 1, 2006; 16(4): 487 - 499. [Abstract] [Full Text] [PDF]

				P. M. Thompson, K. M. Hayashi, S. L. Simon, J. A. Geaga, M. S. Hong, Y. Sui, J. Y. Lee, A. W. Toga, W. Ling, and E. D. London Structural Abnormalities in the Brains of Human Subjects Who Use Methamphetamine J. Neurosci., June 30, 2004; 24(26): 6028 - 6036. [Abstract] [Full Text] [PDF]

				S. Janusonis, V. Gluncic, and P. Rakic Early Serotonergic Projections to Cajal-Retzius Cells: Relevance for Cortical Development J. Neurosci., February 18, 2004; 24(7): 1652 - 1659. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help