title: Intrinsic and extrinsic mechanisms control the termination of cortical interneuron migration.
abstract: During development, neurons migrate from their site of origin to their final destinations. Upon reaching this destination, the termination of their migration is crucial for building functional architectures such as laminated structures and nuclei. How this termination is regulated, however, is not clear. Here, we investigated the contribution of cell-intrinsic mechanisms and extrinsic factors. Using GAD67-GFP knock-in mice and in utero electroporation cell labeling, we visualized GABAergic neurons and analyzed their motility in vitro. We find that the motility of GABAergic neurons in cortical slices gradually decreases as development proceeds and is almost abolished by the end of the first postnatal week. Consistent with this, a reduction of embryonic interneuron motility occurred in dissociated cultures. This is in part due to cell-intrinsic mechanisms, as a reduction in motility is observed during long-term culturing on glial feeder cells. Cell-intrinsic regulation is further supported by observations that interneurons labeled in early stages migrated more actively than those labeled in late stages in the same cortical explant. We found evidence suggesting that upregulation of the potassium-chloride cotransporter KCC2 underlies this intrinsic regulation. Reduced motility is also observed when embryonic interneurons are plated on postnatal cortical feeder cells, suggesting extrinsic factors derived from the postnatal cortex too contribute to termination. These factors should include secreted molecules, as cultured postnatal cortical cells could exercise this effect without directly contacting the interneuron. These findings suggest that intrinsic mechanisms and extrinsic factors coordinate to reduce the motility of migrating neurons, thereby leading to the termination of migration.
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Inamura
authors.forename: Toshiya
authors.initials: T
authors.lastname: Kimura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tada
authors.forename: Takashi
authors.initials: T
authors.lastname: Kurahashi
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Yanagida
authors.forename: Yuchio
authors.initials: Y
authors.lastname: Yanagawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ikenaka
authors.forename: Fujio
authors.initials: F
authors.lastname: Murakami
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D018274:Electroporation; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009457:Neuroglia / Q000502:physiology; D009924:Organ Culture Techniques; D018709:Statistics, Nonparametric; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D000096922:K Cl- Cotransporters
chemical_list: D005968:Glutamate Decarboxylase; D049452:Green Fluorescent Proteins; D027981:Symporters; D000096922:K Cl- Cotransporters; C485184:enhanced green fluorescent protein; C402565:glutamate decarboxylase 1