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Author Notes:

Correspondence: Robert E. Gross, MD, PhD, Department of Neurosurgery, 101 Woodruff Circle, Room 6311, Atlanta, GA 30322; Phone: 404-727-2354; Fax: 404-712-8576; Email: rgross@emory.edu

Acknowledgments: We thank Elizabeth Jackson for her technical assistance and Su Li who conducted the CPP studies.

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Research Funding:

This work was supported by K08 NS46322-01A to R.E.G. E.R.T was partially supported by a Emory University URC and R03 NS048997 grants.

Expression by midbrain dopamine neurons of Sema3A and 3F receptors is associated with chemorepulsion in vitro but a mild in vivo phenotype

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Journal Title:

Molecular and Cellular Neuroscience

Volume:

Volume 44, Number 2

Publisher:

, Pages 135-153

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Here we explore the role of semaphorin 3A and 3F (Sema3A, Sema3F) in the formation of the mesotelencephalic pathway. We show that Sema3A and 3F are expressed in the ventral mesencephalon (VM) of E13.5 rat embryos; the receptors Neuropilin 1 and Neuropilin 2, and coreceptors L1CAM, NrCAM, and Plexins A1 and A3 but not A4 are expressed by VM dopaminergic neurons; these neurons bind Sema3A and 3F in vitro which induces collapse of their growth cones and elicits, with different potencies, a repulsive response; and this response is absent in axons from Nrp1 and Nrp2 null embryos. Despite these in vitro effects, only very mild anatomical defects were detected in the organization of the mesotelencephalic pathway in embryonic and adult Nrp1 or Nrp2 null mice. However, the dopaminergic meso-habenular pathway and catecholaminergic neurons in the parafascicular and paraventricular nuclei of the thalamus were significantly affected in Nrp2 null mice. These data are consistent with a model whereby Sema3A and 3F, in combination with other guidance molecules, contributes to the navigation of DA axons to their final synaptic targets.

Copyright information:

© 2010 Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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