Role of neuropilin-2 in the ipsilateral growth of midbrain dopaminergic axons
Autor: | Makio Torigoe, Atsu Aiba, Valérie Castellani, Ikuo Matsuda, Atsushi Tamada, Fujio Murakami, Kenta Yamauchi |
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Rok vydání: | 2011 |
Předmět: |
Transcription
Genetic Nerve Tissue Proteins Semaphorins Biology Midbrain Diencephalon Mice Semaphorin ROBO1 Mesencephalon SLIT1 medicine SLIT2 Animals Axon Cells Cultured Mice Knockout General Neuroscience Dopaminergic Neurons Membrane Proteins Slit Axons Neuropilin-2 Mice Inbred C57BL medicine.anatomical_structure nervous system Mutation Intercellular Signaling Peptides and Proteins Neuroscience |
Zdroj: | The European journal of neuroscience. 37(10) |
ISSN: | 1460-9568 |
Popis: | Axonal projections in the CNS can be categorized as either crossed or uncrossed. Crossing and uncrossing of axons has been explained by attractive and repulsive molecules like Netrin-1 and Slits, which are secreted by midline structures. However, uncrossed projections can be established even in double knockout mice of slit1 and slit2 or of roundabout1 (robo1) and robo2, two receptors for Slits. Here, we found that a novel mechanism mediated by Neuropilin-2 (Nrp2) contributes to the formation of uncrossed projections of midbrain dopaminergic neurons (mDANs). Nrp2 transcriptional activities were detected in a subset of mDANs, and its protein was expressed in mDAN axons growing through the ipsilateral diencephalon. In nrp2(lac) (Z) (/lac) (Z) mice, mDAN axons aberrantly grew toward the ventral midline and even crossed it, suggesting that Nrp2 is necessary for the development of mDAN ipsilateral projections. We investigated the involvement of Semaphorin 3B (Sema3B) and Sema3F, two ligands of Nrp2, by analysing mDAN axon trajectories in single or double knockout mice. In both cases, mDAN axons still projected ipsilaterally, suggesting the involvement mechanisms independent of these Sema3s. Nrp2-deficient mDAN axons retained their responsiveness to Slit2, demonstrating that aberrant mDAN axons in nrp2(lac) (Z) (/lac) (Z) mice were not indirectly mediated by alterations in Slit/Robo signaling. Taken together, our results indicate that a novel mechanism mediated by Nrp2 contributes to the establishment of uncrossed projections by mDAN axons. |
Databáze: | OpenAIRE |
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