title: Arl13b in primary cilia regulates the migration and placement of interneurons in the developing cerebral cortex.
abstract: Coordinated migration and placement of interneurons and projection neurons lead to functional connectivity in the cerebral cortex; defective neuronal migration and the resultant connectivity changes underlie the cognitive defects in a spectrum of neurological disorders. Here we show that primary cilia play a guiding role in the migration and placement of postmitotic interneurons in the developing cerebral cortex and that this process requires the ciliary protein, Arl13b. Through live imaging of interneuronal cilia, we show that migrating interneurons display highly dynamic primary cilia and we correlate cilia dynamics with the interneuron's migratory state. We demonstrate that the guidance cue receptors essential for interneuronal migration localize to interneuronal primary cilia, but their concentration and dynamics are altered in the absence of Arl13b. Expression of Arl13b variants known to cause Joubert syndrome induce defective interneuronal migration, suggesting that defects in cilia-dependent interneuron migration may in part underlie the neurological defects in Joubert syndrome patients.
authors.affiliation: UNC Neuroscience Center and the Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Holden
authors.initials: H
authors.lastname: Higginbotham
authors.forename: Tae-Yeon
authors.initials: TY
authors.lastname: Eom
authors.forename: Laura E
authors.initials: LE
authors.lastname: Mariani
authors.forename: Amelia
authors.initials: A
authors.lastname: Bachleda
authors.forename: Joshua
authors.initials: J
authors.lastname: Hirt
authors.forename: Vladimir
authors.initials: V
authors.lastname: Gukassyan
authors.forename: Corey L
authors.initials: CL
authors.lastname: Cusack
authors.forename: Cary
authors.initials: C
authors.lastname: Lai
authors.forename: Tamara
authors.initials: T
authors.lastname: Caspary
authors.forename: E S
authors.initials: ES
authors.lastname: Anton
mesh_terms: D020727:ADP-Ribosylation Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000015:Abnormalities, Multiple; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002526:Cerebellar Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D002531:Cerebellum / Q000002:abnormalities; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000254:growth & development* / Q000502:physiology*; D002923:Cilia / Q000502:physiology*; D005124:Eye Abnormalities / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007395:Interneurons / Q000502:physiology*; D052177:Kidney Diseases, Cystic / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D050505:Mutant Proteins / Q000235:genetics / Q000502:physiology; D012160:Retina / Q000002:abnormalities / Q000473:pathology / Q000503:physiopathology
chemical_list: C560093:Arl13b protein, mouse; D050505:Mutant Proteins; D020727:ADP-Ribosylation Factors; C530391:ARL13B protein, human