title: Cdk5 phosphorylation of ErbB4 is required for tangential migration of cortical interneurons.
abstract: Interneuron dysfunction in humans is often associated with neurological and psychiatric disorders, such as epilepsy, schizophrenia, and autism. Some of these disorders are believed to emerge during brain formation, at the time of interneuron specification, migration, and synapse formation. Here, using a mouse model and a host of histological and molecular biological techniques, we report that the signaling molecule cyclin-dependent kinase 5 (Cdk5), and its activator p35, control the tangential migration of interneurons toward and within the cerebral cortex by modulating the critical neurodevelopmental signaling pathway, ErbB4/phosphatidylinositol 3-kinase, that has been repeatedly linked to schizophrenia. This finding identifies Cdk5 as a crucial signaling factor in cortical interneuron development in mammals.
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1 6BT, UK.
authors.forename: Sonja
authors.initials: S
authors.lastname: Rakić
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kanatani
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1 6BT, UK.
authors.forename: David
authors.initials: D
authors.lastname: Hunt
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1 6BT, UK.
authors.forename: Clare
authors.initials: C
authors.lastname: Faux
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1 6BT, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Cariboni
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1 6BT, UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Chiara
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1 6BT, UK.
authors.forename: Shabana
authors.initials: S
authors.lastname: Khan
authors.affiliation: Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London SW3 6JB, UK.
authors.forename: Olivia
authors.initials: O
authors.lastname: Wansbury
authors.affiliation: Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London SW3 6JB, UK.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Howard
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Department of Cellular and Molecular Neuroscience, Imperial College School of Medicine, London W12 0NN, UK.
authors.forename: Margareta
authors.initials: M
authors.lastname: Nikolić
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1 6BT, UK.
authors.forename: John G
authors.initials: JG
authors.lastname: Parnavelas
mesh_terms: D000818:Animals; D019556:COS Cells; D002465:Cell Movement / Q000502:physiology*; D002540:Cerebral Cortex / Q000196:embryology / Q000502:physiology*; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics / Q000378:metabolism*; D059330:GABAergic Neurons / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D007395:Interneurons / Q000502:physiology*; D007633:Keratins / Q000378:metabolism; D008822:Mice, Transgenic; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism; D066247:Receptor, ErbB-4 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C492236:Cdk5r1 protein, mouse; D007633:Keratins; D010770:Phosphotransferases; D058539:Phosphatidylinositol 3-Kinase; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
keywords: cerebral cortex; interneurons; migration; mouse; phosphorylation