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Neuron. 2014 Jul 16;83(2):372-387. doi: 10.1016/j.neuron.2014.05.036.

Subdomain-mediated axon-axon signaling and chemoattraction cooperate to regulate afferent innervation of the lateral habenula.

Author information

1
Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
2
Proteomics Centre and Department of Cell Biology, Erasmus University Medical Centre, Dr Molewaterplein 50, 3015 GE Rotterdam, the Netherlands.
3
Department of Basic Science, Faculty of Medicine, University of Crete and Institute of Molecular Biology and Biotechnology, Vassilika Vouton, Heraklion GR-7110, Greece.
4
Queensland Brain Institute and The School of Biomedical Sciences, University of Queensland, Building 79, St Lucia Campus, Brisbane, QLD 4067, Australia.
5
Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, 50411 Tartu, Estonia.
6
Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands. Electronic address: r.j.pasterkamp@umcutrecht.nl.

Abstract

A dominant feature of neural circuitry is the organization of neuronal projections and synapses into specific brain nuclei or laminae. Lamina-specific connectivity is controlled by the selective expression of extracellular guidance and adhesion molecules in the target field. However, how (sub)nucleus-specific connections are established and whether axon-derived cues contribute to subdomain targeting are largely unknown. Here, we demonstrate that the lateral subnucleus of the habenula (lHb) determines its own afferent innervation by sending out efferent projections that express the cell adhesion molecule LAMP to reciprocally collect and guide dopaminergic afferents to the lHb-a phenomenon we term subdomain-mediated axon-axon signaling. This process of reciprocal axon-axon interactions cooperates with lHb-specific chemoattraction mediated by Netrin-1, which controls axon target entry, to ensure specific innervation of the lHb. We propose that cooperation between pretarget reciprocal axon-axon signaling and subdomain-restricted instructive cues provides a highly precise and general mechanism to establish subdomain-specific neural circuitry.

PMID:
25033181
DOI:
10.1016/j.neuron.2014.05.036
[Indexed for MEDLINE]
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