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Cerebral Cortex Advance Access originally published online on May 11, 2009
Cerebral Cortex 2009 19(Supplement 1):i144-i151; doi:10.1093/cercor/bhp035
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© 2009 The Authors
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

This article appears in the following Cerebral Cortex issue: Cortical Development: Neural Stem Cells to Neural Circuits Chania, Greece, May 22-25, 2008 [View the issue table of contents]

Slits Are Chemorepellents Endogenous to Hypothalamus and Steer Thalamocortical Axons into Ventral Telencephalon

Janet E. Braisted1, Thomas Ringstedt1,2 and Dennis D. M. O'Leary1

1 Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, CA 92037, USA

Address correspondence to Dennis D. M. O'Leary, Molecular Neurobiology Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Email: doleary{at}salk.edu.

Thalamocortical axons (TCAs) originate in dorsal thalamus, extend ventrally along the lateral thalamic surface, and as they approach hypothalamus make a lateral turn into ventral telencephalon. In vitro studies show that hypothalamus releases a chemorepellent for TCAs, and analyses of knockout mice indicate that Slit chemorepellents and their receptor Robo2 influence TCA pathfinding. We show that Slit chemorepellents are the hypothalamic chemorepellent and act through Robos to steer TCAs into ventral telencephalon. During TCA pathfinding, Slit1 and Slit2 are expressed in hypothalamus and ventral thalamus and Robo1 and Robo2 are expressed in dorsal thalamus. In collagen gel cocultures of dorsal thalamus and Slit2-expressing cells, axon number and length are decreased on the explant side facing Slit2-expressing cells, overall axon outgrowth is diminished, and axons turn away from the Slit2-expressing cells. Thus, Slit2 is an inhibitor and chemorepellent for dorsal thalamic axons. Collagen gel cocultures of dorsal thalamus with sections of live diencephalon, with and without the hypothalamus portion overlaid with Robo2-fc-expressing cells to block Slit function, identify Slits as the hypothalamic chemorepellent. Thus, Slits are chemorepellents for TCAs endogenous to hypothalamus and steer TCAs from diencephalon into ventral telencephalon, a critical pathfinding event defective in Slit and Robo2 mutant mice.

Key Words: axon guidance • axon inhibition • dorsal thalamus • hypothalamus • internal capsule • neocortex • robos

2 Current address: Karolinska Institute, Neonatal Research Unit, Astrid Lindgren Children's Hospital, Stockholm, Sweden

The authors contributed equally to this work.


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