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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 7, 2009, 29(40):12542-12557; doi:10.1523/JNEUROSCI.2521-09.2009

This Article Full Text Full Text (PDF) Supplemental Data 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 Web of Science Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Kolk, S. M. Articles by Pasterkamp, R. J. PubMed Articles by Kolk, S. M. Articles by Pasterkamp, R. J.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Semaphorin 3F Is a Bifunctional Guidance Cue for Dopaminergic Axons and Controls Their Fasciculation, Channeling, Rostral Growth, and Intracortical Targeting

Sharon M. Kolk,¹ Rou-Afza F. Gunput,¹ Tracy S. Tran,² Dianne M. A. van den Heuvel,¹ Asheeta A. Prasad,¹ Anita J. C. G. M. Hellemons,¹ Youri Adolfs,¹ David D. Ginty,² Alex L. Kolodkin,² J. Peter H. Burbach,¹ Marten P. Smidt,¹ and R. Jeroen Pasterkamp¹

¹Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands, and ²The Solomon H. Snyder Department of Neuroscience and Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Correspondence should be addressed to either Sharon M. Kolk at her present address or R. Jeroen Pasterkamp, Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands, Email: S.Kolk{at}ncmls.ru.nl or Email: r.j.pasterkamp{at}umcutrecht.nl

Dopaminergic neurons in the mesodiencephalon (mdDA neurons) make precise synaptic connections with targets in the forebrain via the mesostriatal, mesolimbic, and mesoprefrontal pathways. Because of the functional importance of these remarkably complex ascending axon pathways and their implication in human disease, the mechanisms underlying the development of these connections are of considerable interest. Despite extensive in vitro studies, the molecular determinants that ensure the perfect formation of these pathways in vivo remain mostly unknown. Here, we determine the embryonic origin and ontogeny of the mouse mesoprefrontal pathway and use these data to reveal an unexpected requirement for semaphorin 3F (Sema3F) and its receptor neuropilin-2 (Npn-2) during mdDA pathway development using tissue culture approaches and analysis of sema3F^–/–, npn-2^–/–, and npn-2^–/–;TH-Cre mice. We show that Sema3F is a bifunctional guidance cue for mdDA axons, some of which have the remarkable ability to regulate their responsiveness to Sema3F as they develop. During early developmental stages, Sema3F chemorepulsion controls previously uncharacterized aspects of mdDA pathway development through both Npn-2-dependent (axon fasciculation and channeling) and Npn-2-independent (rostral growth) mechanisms. Later on, chemoattraction mediated by Sema3F and Npn-2 is required to orient mdDA axon projections in the cortical plate of the medial prefrontal cortex. This latter finding demonstrates that regulation of axon orientation in the target field occurs by chemoattractive mechanisms, and this is likely to also apply to other neural systems. In all, this study provides a framework for additional dissection of the molecular basis of mdDA pathway development and disease.

---

Received May 31, 2009; revised Aug. 10, 2009; accepted Sept. 1, 2009.

Correspondence should be addressed to either Sharon M. Kolk at her present address or R. Jeroen Pasterkamp, Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands, Email: S.Kolk{at}ncmls.ru.nl or Email: r.j.pasterkamp{at}umcutrecht.nl

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help