Neuregulin 3 Mediates Cortical Plate Invasion and Laminar Allocation of GABAergic Interneurons.
Neural circuits in the cerebral cortex consist of excitatory pyramidal cells and inhibitory interneurons. These two main classes of cortical neurons follow largely different genetic programs, yet they assemble into highly specialized circuits during development following a very precise choreography. Previous studies have shown that signals produced by pyramidal cells influence the migration of cortical interneurons, but the molecular nature of these factors has remained elusive. Here, we identified Neuregulin 3 (Nrg3) as a chemoattractive factor expressed by developing pyramidal cells that guides the allocation of cortical interneurons in the developing cortical plate. Gain- and loss-of-function approaches reveal that Nrg3 modulates the migration of interneurons into the cortical plate in a process that is dependent on the tyrosine kinase receptor ErbB4. Perturbation of Nrg3 signaling in conditional mutants leads to abnormal lamination of cortical interneurons. Nrg3 is therefore a critical mediator in the assembly of cortical inhibitory circuits.
Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK; Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas & Universidad Miguel Hernández, Sant Joan d'Alacant 03550, Spain.
Giorgia
G
Bartolini
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas & Universidad Miguel Hernández, Sant Joan d'Alacant 03550, Spain.
Juan Antonio
JA
Sánchez-Alcañiz
Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK; MRC Centre for Neurodevelopmental Disorders, King's College London, London SE1 1UL, UK.
Catarina
C
Osório
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas & Universidad Miguel Hernández, Sant Joan d'Alacant 03550, Spain.
Manuel
M
Valiente
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas & Universidad Miguel Hernández, Sant Joan d'Alacant 03550, Spain.
Cristina
C
García-Frigola
Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK; MRC Centre for Neurodevelopmental Disorders, King's College London, London SE1 1UL, UK; Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas & Universidad Miguel Hernández, Sant Joan d'Alacant 03550, Spain. Electronic address: oscar.marin@kcl.ac.uk.
Oscar
O
Marín
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism; D059330:GABAergic Neurons / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020880:Neuregulins; D017966:Pyramidal Cells / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D066247:Receptor, ErbB-4 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D047908:Intracellular Signaling Peptides and Proteins; D020880:Neuregulins; C108113:Nrg3 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D066247:Receptor, ErbB-4
Erbb4; GABA; cerebral cortex; cortical plate; inhibition; interneuron; lamination; migration; neuregulins; pyramidal cell