title: Role of neuropilin-2 in the ipsilateral growth of midbrain dopaminergic axons.
abstract: 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.
authors.affiliation: Laboratory of Neuroscience, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
authors.forename: Makio
authors.initials: M
authors.lastname: Torigoe
authors.forename: Kenta
authors.initials: K
authors.lastname: Yamauchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tamada
authors.forename: Ikuo
authors.initials: I
authors.lastname: Matsuda
authors.forename: Atsu
authors.initials: A
authors.lastname: Aiba
authors.forename: Valérie
authors.initials: V
authors.lastname: Castellani
authors.forename: Fujio
authors.initials: F
authors.lastname: Murakami
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D039943:Neuropilin-2 / Q000235:genetics* / Q000378:metabolism; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D000098552:Slit Homolog 2 Protein
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D039943:Neuropilin-2; C526269:Sema3b protein, mouse; C491229:Sema3f protein, mouse; D039961:Semaphorins; D000098552:Slit Homolog 2 Protein