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.
Highlights
Dysfunction of cerebral cortical interneurons, which may stem from their abnormal development and migration, has been implicated in the etiology of a number of neurological and psychiatric disorders in humans, such as epilepsy, schizophrenia, and autism (Marín 2012)
The differential expression of ErbB growth factor receptors, their ligands, and associated signaling molecules in embryonic (E) forebrain or its GABAergic and non-GABAergic cells, isolated from the WTGAD67GFP mice by Fluorescence-Activated Cell Sorting (FACS) (Fig. 1A), was first explored, bearing in mind that some ErbBs are cyclin-dependent kinase 5 (Cdk5) substrates (Fu et al 2001; Li et al 2003; Fu et al 2005), and that ErbB4 is expressed in migrating interneurons (Yau et al 2003)
We discovered that cortical interneurons utilize specific ErbB4mediated signaling pathways to regulate their motility while coursing toward and through forebrain areas enriched in NRG1, NRG3, and HB-epidermal growth factor (EGF)
Summary
Dysfunction of cerebral cortical interneurons, which may stem from their abnormal development and migration, has been implicated in the etiology of a number of neurological and psychiatric disorders in humans, such as epilepsy, schizophrenia, and autism (Marín 2012). It has been found that interneurons of the cerebral cortex (Cx) originate mainly from the subcortical ganglionic eminence (GE) and follow a long journey to their final destinations in the Cx. Initially, interneurons travel in multiple tangential streams, before turning radially to settle in the correct layer. Interneurons travel in multiple tangential streams, before turning radially to settle in the correct layer Evidence suggests that their migration relies on the dynamics of the branched leading processes that efficiently modify their orientation in response to extracellular guidance cues (Ang et al 2003; Métin et al 2006; Marin et al 2010). Little is known about the signaling molecules, linking external guidance cues, and cytoskeletal responses, crucial for proper interneuron migration into the Cx
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
