title: Pax6-dependent boundary defines alignment of migrating olfactory cortex neurons via the repulsive activity of ephrin A5.
abstract: Neuronal migration is a prerequisite event for the establishment of highly ordered neuronal circuits in the developing brain. Here, we report Pax6-dependent alignment of the olfactory cortex neurons in the developing telencephalon. These neurons were generated in the dorsal part of telencephalon, migrated ventrally and stopped at the pallium-subpallium boundary (PSB). In Pax6 mutant rat embryos, however, these neurons invaded the ventral part of the telencephalon by crossing the PSB. Ephrin A5, one of the ligands for EphA receptors, was specifically expressed in the ventral part of the telencephalon, and its expression level was markedly reduced in the Pax6 mutant. Gain- and loss-of-function studies of ephrin A5 indicated that ephrin A5 plays an important role in the alignment of olfactory cortex neurons at the PSB. Our results suggest that Pax6-regulated ephrin A5 acts as a repulsive molecule for olfactory cortex neurons in the developing telencephalon.
authors.affiliation: Division of Developmental Neuroscience, Center for Translational and Advanced Animal Research CTTAR, Seiryo-machi, 980-8575, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nomura
authors.forename: Johan
authors.initials: J
authors.lastname: Holmberg
authors.forename: Jonas
authors.initials: J
authors.lastname: Frisen
authors.forename: Noriko
authors.initials: N
authors.lastname: Osumi
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002540:Cerebral Cortex; D015536:Down-Regulation; D036386:Ephrin-A5 / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008954:Models, Biological; D009154:Mutation; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D036386:Ephrin-A5; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605733:Pax6 protein, rat; D012097:Repressor Proteins