Neuregulin 3 Mediates Cortical Plate Invasion and Laminar Allocation of GABAergic Interneurons

Publication date: 31 January 2017
Source:Cell Reports, Volume 18, Issue 5
Author(s): Giorgia Bartolini, Juan Antonio Sánchez-Alcañiz, Catarina Osório, Manuel Valiente, Cristina García-Frigola, Oscar Marín
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.

Graphical abstract

Teaser

The integration of interneurons in the developing cerebral cortex depends on signals generated by pyramidal cells. In this study, Bartolini et al. identify Neuregulin 3 as a developmentally regulated factor that controls the migration of interneurons into the cortical plate and influences their final laminar distribution.


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