title: Hardwiring the brain: endocannabinoids shape neuronal connectivity.
abstract: The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB(1) cannabinoid receptors (CB(1)Rs) are enriched in the axonal growth cones of gamma-aminobutyric acid-containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB(1)R internalization and elimination from filopodia and induce chemorepulsion and collapse of axonal growth cones of these GABAergic interneurons by activating RhoA. Similarly, endocannabinoids diminish the galvanotropism of Xenopus laevis spinal neurons. These findings, together with the impaired target selection of cortical GABAergic interneurons lacking CB(1)Rs, identify endocannabinoids as axon guidance cues and demonstrate that endocannabinoid signaling regulates synaptogenesis and target selection in vivo.
authors.affiliation: Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-17177 Stockholm, Sweden.
authors.forename: Paul
authors.initials: P
authors.lastname: Berghuis
authors.forename: Ann M
authors.initials: AM
authors.lastname: Rajnicek
authors.forename: Yury M
authors.initials: YM
authors.lastname: Morozov
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Ross
authors.forename: Jan
authors.initials: J
authors.lastname: Mulder
authors.forename: Gabriella M
authors.initials: GM
authors.lastname: Urbán
authors.forename: Krisztina
authors.initials: K
authors.lastname: Monory
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marsicano
authors.forename: Michela
authors.initials: M
authors.lastname: Matteoli
authors.forename: Alison
authors.initials: A
authors.lastname: Canty
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Irving
authors.forename: István
authors.initials: I
authors.lastname: Katona
authors.forename: Yuchio
authors.initials: Y
authors.lastname: Yanagawa
authors.forename: Pasko
authors.initials: P
authors.lastname: Rakic
authors.forename: Beat
authors.initials: B
authors.lastname: Lutz
authors.forename: Ken
authors.initials: K
authors.lastname: Mackie
authors.forename: Tibor
authors.initials: T
authors.lastname: Harkany
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000648:ultrastructure; D063388:Endocannabinoids; D020439:Growth Cones / Q000000981:diagnostic imaging / Q000502:physiology; D017403:In Situ Hybridization; D007395:Interneurons / Q000000981:diagnostic imaging / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000502:physiology*; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D013569:Synapses / Q000000981:diagnostic imaging / Q000502:physiology; D014463:Ultrasonography; D029867:Xenopus Proteins / Q000502:physiology; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1; D029867:Xenopus Proteins; D005680:gamma-Aminobutyric Acid