The DOI matches its Crossref record; 76 of the 77 references it cites were found in a registry or an index.
Semaphorin 3F Is a Bifunctional Guidance Cue for Dopaminergic Axons and Controls Their Fasciculation, Channeling, Rostral Growth, and Intracortical Targeting
Open accessAbstract
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.
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“A subset of the medial part of the ventral tegmental area (VTA) starts to project to prefrontal subdomains around E15/E16 (rodent) and week 10–13 in human [155–158].”
From Development of prefrontal cortex (2022) · cites this paper as [156]
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“while Semaphorin3F is orchestrating their fasciculation, rostral growth and targeting within the various mPFC subdomains [156].”
From Development of prefrontal cortex (2022) · cites this paper as [156]
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Citations
Cites
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“In the adult mouse, mesoprefrontal mdDA projections originate in the medial VTA (Fallon, 1981; Swanson, 1982; Margolis et al., 2006; Lammel et al., 2008).”
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Development of prefrontal cortex
Kolk, S. M., & Rakic, P. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-021-01137-9 · Cited by 378
“Steering dopaminergic projections from the VTA via the medial forebrain bundle toward forebrain regions mostly depend on a coordinated action of the guidance molecules Dcc and Netrin-1 mediated by microRNA miR-218 control of Dcc expression in the VTA [159–161], while Semaphorin3F is orchestrating their fasciculation,…”
BackgroundSelf-citationC 9orf72 ablation in mice does not cause motor neuron degeneration or motor deficits
Koppers, M., Blokhuis, A. M., Westeneng, H., Terpstra, M. L., Zundel, C. A. C., de Sá, R. V., Schellevis, R. D., Waite, A. J., Blake, D. J., Veldink, J. H., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24453 · Cited by 301
Self-citationGetting neural circuits into shape with semaphorins
Pasterkamp, R. J. (2012) · Nature reviews. Neuroscience · doi:10.1038/nrn3302 · Cited by 281
Self-citationMidbrain dopaminergic neurons: A review of the molecular circuitry that regulates their development
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Metadata
- Authors
- 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., Adolfs, Y., Ginty, D. D., Kolodkin, A. L., Burbach, J. P. H., Smidt, M. P., & Pasterkamp, R. J.
- Affiliations
- University Medical Center Utrecht (NL)
- Utrecht University (NL)
- Howard Hughes Medical Institute (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-10-07
- Volume
- 29
- Issue
- 40
- Pages
- 12542-12557
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3097132
- OpenAlex
- W2142820387
- Cited by
- 114
- References
- 77
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 8 · 2020: 7 · 2019: 8 · 2018: 3 · 2017: 13 · 2016: 2 · 2015: 8 · 2014: 6 · 2013: 11 · 2012: 12
- FWCI
- 3.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Funders
- Howard Hughes Medical Institute
- National Alliance for Research on Schizophrenia and Depression
- Parkinsonfonden
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- SEMA3F, neuropilin-2, axon fasciculation, chemoattraction, chemorepulsion, axon targeting, medial prefrontal cortex, axon orientation, dopaminergic neuron development
- MeSH terms
- Animals, Axons, Diencephalon, Dopamine, Immunohistochemistry, Membrane Proteins, Mice, Inbred C57BL, Mice, Mutant Strains, Nerve Tissue Proteins, Neurons, Neurites, Prosencephalon, Body Patterning, Protein Transport, Neuropilin-2, Tissue Culture Techniques, Mice
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