Frizzled3 Controls Axonal Polarity and Intermediate Target Entry during Striatal Pathway Development
| Autor: | Youri Adolfs, R. Jeroen Pasterkamp, Noelia Antón-Bolaños, Asheeta A. Prasad, Eduardo Leyva-Díaz, Kati Rehberg, Renata Baptista Vieira de Sá, Guillermina López-Bendito, Francesca Morello, Fadel Tissir |
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| Přispěvatelé: | Netherlands Organisation for Health Research and Development, Parkinson's Disease Foundation, European Commission, Agence Nationale de la Recherche (France), Ministerio de Economía y Competitividad (España), EMBO |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Neuroscience(all) Mice Transgenic Guidepost cells Striatum Development Biology Research Support Globus Pallidus Mice Brain Nucleus Cell polarity Neural Pathways Journal Article medicine Animals Humans Axon Non-U.S. Gov't Cells Cultured Homeodomain Proteins Neurons Receptors Dopamine D2 Research Support Non-U.S. Gov't Axon guidance General Neuroscience Cell Polarity Receptor Protein-Tyrosine Kinases Articles Frizzled3 Embryo Mammalian Axons Corpus Striatum Frizzled Receptors Mice Inbred C57BL medicine.anatomical_structure Globus pallidus HEK293 Cells nervous system Forebrain Female sense organs Neuroscience Corridor cell Transcription Factors |
| Zdroj: | Journal of Neuroscience, 35(42), 14205. Society for Neuroscience |
| ISSN: | 0270-6474 |
| Popis: | The striatum is a large brain nucleus with an important role in the control of movement and emotions. Medium spiny neurons (MSNs) are striatal output neurons forming prominent descending axon tracts that target different brain nuclei. However, how MSN axon tracts in the forebrain develop remains poorly understood. Here, we implicate the Wnt binding receptor Frizzled3 in several uncharacterized aspects of MSN pathway formation [i.e., anterior–posterior guidance of MSN axons in the striatum and their subsequent growth into the globus pallidus (GP), an important (intermediate) target]. In Frizzled3 knock-out mice, MSN axons fail to extend along the anterior–posterior axis of the striatum, and many do not reach the GP. Wnt5a acts as an attractant for MSN axons in vitro, is expressed in a posterior high, anterior low gradient in the striatum, and Wnt5a knock-out mice phenocopy striatal anterior–posterior defects observed in Frizzled3 mutants. This suggests that Wnt5a controls anterior–posterior guidance of MSN axons through Frizzled3. Axons that reach the GP in Frizzled3 knock-out mice fail to enter this structure. Surprisingly, entry of MSN axons into the GP non–cell-autonomously requires Frizzled3, and our data suggest that GP entry may be contingent on the correct positioning of “corridor” guidepost cells for thalamocortical axons by Frizzled3. Together, these data dissect MSN pathway development and reveal (non)cell-autonomous roles for Frizzled3 in MSN axon guidance. Further, they are the first to identify a gene that provides anterior–posterior axon guidance in a large brain nucleus and link Frizzled3 to corridor cell development. This work was supported by The Netherlands Organization for Health Research and Development (ZonMW-VIDI and ZonMW-TOP), Stichting ParkinsonFonds, and the European Union (mdDANeurodev, FP7/2007–2011, Grant 222999) to R.J.P., Actions de Recherches Concerteés (ARC-10/15-026) and Fondation médicale Reine Elisabeth to F.T., and the Spanish MINECO BFU2012-34298 to G.L.-B. (who is an EMBO Young Investigator). This study was performed in part within the framework of Dutch Top Institute Pharma Project T5-207 to R.J.P. |
| Databáze: | OpenAIRE |
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