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A molecular switch helps interneurons find their way in the cortex

Researchers from King’s College London have identified a molecule which attracts interneurons as they migrate within the developing cortex.

The study, published in Cell Reports, provides key insights into how interneurons position within the developing cortex and how this puzzle comes together, which is fundamental for the building of functional brain networks.

During development, cortical interneurons invade the cortex following two tangential migratory streams within the developing cortex, one superficial and one deep, but largely avoid the place where they finally reside, known as the cortical plate. The initial avoidance of this area is thought to be important for the normal dispersion of interneurons throughout the entire cerebral cortex, but the mechanisms that regulate the tangential to radial switch in the migration of cortical interneurons and the subsequent invasion of the cortical plate were largely unknown, until now.

In this article, researchers from the Centre for Developmental Neurobiology (CDN) at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) and the MRC Centre for Neurodevelopmental Disorders (MRC CNDD), King’s College London, led by Professor Oscar Marín, report the identification of a molecule, known as Neuregulin 3 (Nrg3), that functions as a chemoattractive factor for migrating interneurons. Nrg3 expression is confined to the developing cortical plate, thereby guiding the positioning of cortical interneurons into this region. While previous studies have shown that signals produced by pyramidal cells influence the migration of cortical interneurons, this is the first time that the molecular nature of these factors has been revealed. The study by Giorgia Bartolini and colleagues shows that pyramidal cells attract interneurons into the cortical plate through a mechanism mediated by Nrg3.

This work was supported by grants from the European Research Council and the Spanish Government.

Paper reference: Bartolini, G et al (2017) Neuregulin 3 mediates cortical plate invasion and laminar allocation of GABAergic interneurons Cell Reports