Semaphorin 3F is a bifunctional guidance cue for dopaminergic axons and controls their fasciculation, channeling, rostral growth, and intracortical targeting

Sharon M. Kolk, Rou Afza F Gunput, Tracy S. Tran, Dianne M A Van Den Heuvel, Asheeta A. Prasad, Anita J C G M Hellemons, Youri Adolfs, David D. Ginty, Alex L Kolodkin, J. Peter H Burbach, Marten P. Smidt, R. Jeroen Pasterkamp

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)12542-12557
Number of pages16
JournalJournal of Neuroscience
Volume29
Issue number40
DOIs
StatePublished - Oct 7 2009

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Semaphorins
Fasciculation
Neuropilin-2
Cues
Axons
Growth
Aptitude
Dopaminergic Neurons
Prosencephalon
Prefrontal Cortex
Cerebral Cortex
Dissection
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kolk, S. M., Gunput, R. A. F., Tran, T. S., Van Den Heuvel, D. M. A., Prasad, A. A., Hellemons, A. J. C. G. M., ... Pasterkamp, R. J. (2009). Semaphorin 3F is a bifunctional guidance cue for dopaminergic axons and controls their fasciculation, channeling, rostral growth, and intracortical targeting. Journal of Neuroscience, 29(40), 12542-12557. https://doi.org/10.1523/JNEUROSCI.2521-09.2009

Semaphorin 3F is a bifunctional guidance cue for dopaminergic axons and controls their fasciculation, channeling, rostral growth, and intracortical targeting. / Kolk, Sharon M.; Gunput, Rou Afza F; Tran, Tracy S.; Van Den Heuvel, Dianne M A; Prasad, Asheeta A.; Hellemons, Anita J C G M; Adolfs, Youri; Ginty, David D.; Kolodkin, Alex L; Burbach, J. Peter H; Smidt, Marten P.; Pasterkamp, R. Jeroen.

In: Journal of Neuroscience, Vol. 29, No. 40, 07.10.2009, p. 12542-12557.

Research output: Contribution to journalArticle

Kolk, SM, Gunput, RAF, Tran, TS, Van Den Heuvel, DMA, Prasad, AA, Hellemons, AJCGM, Adolfs, Y, Ginty, DD, Kolodkin, AL, Burbach, JPH, Smidt, MP & Pasterkamp, RJ 2009, 'Semaphorin 3F is a bifunctional guidance cue for dopaminergic axons and controls their fasciculation, channeling, rostral growth, and intracortical targeting', Journal of Neuroscience, vol. 29, no. 40, pp. 12542-12557. https://doi.org/10.1523/JNEUROSCI.2521-09.2009
Kolk, Sharon M. ; Gunput, Rou Afza F ; Tran, Tracy S. ; Van Den Heuvel, Dianne M A ; Prasad, Asheeta A. ; Hellemons, Anita J C G M ; Adolfs, Youri ; Ginty, David D. ; Kolodkin, Alex L ; Burbach, J. Peter H ; Smidt, Marten P. ; Pasterkamp, R. Jeroen. / Semaphorin 3F is a bifunctional guidance cue for dopaminergic axons and controls their fasciculation, channeling, rostral growth, and intracortical targeting. In: Journal of Neuroscience. 2009 ; Vol. 29, No. 40. pp. 12542-12557.
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AU - Hellemons, Anita J C G M

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