In the cerebral cortex, pyramidal cells and interneurons are generated in distant germinal zones, and so the mechanisms that control their precise assembly into specific microcircuits remain an enigma. Here we report that cortical interneurons labeled at the clonal level do not distribute randomly but rather have a strong tendency to cluster in the mouse neocortex. This behavior is common to different classes of interneurons, independently of their origin. Interneuron clusters are typically contained within one or two adjacent cortical layers, are largely formed by isochronically generated neurons and populate specific layers, as revealed by unbiased hierarchical clustering methods. Our results suggest that different progenitor cells give rise to interneurons populating infra- and supragranular cortical layers, which challenges current views of cortical neurogenesis. Thus, specific lineages of cortical interneurons seem to be produced to primarily mirror the laminar structure of the cerebral cortex, rather than its columnar organization.
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We thank A. Casillas, T. Gil and M. Pérez for excellent technical assistance, D. Gelman for contributing to the development of conditional retroviruses, S.A. Anderson (University of Pennsylvania School of Medicine; Nkx2-1-Cre), S. Arber (University of Basel; PV-Cre), and A. Barco (Instituto de Neurociencias; Nestin-Cre) for mouse strains, F.H. Gage (The Salk Institute for Biological Studies) for retroviral vectors and N. Tamamaki (Kumamoto University) for the CAG-Fucci-G plasmid. We are grateful to members of the Marín and Rico laboratories for discussions and ideas. Supported by grants from Spanish Ministry of Economy and Innovation (MINECO) SAF2011-28845 to O.M., BFU2011-23049 to M.M. and CONSOLIDER CSD2007-00023 to O.M. and M.M., and from the European Research Council (ERC-2011-AdG 293683) to O.M. G.C. and I.S. are recipients of “Formación de Personal Investigador” (FPI) fellowships from the MINECO. N.D. is the recipient of a European Molecular Biology Organization (EMBO) long-term fellowship.
The authors declare no competing financial interests.
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Ciceri, G., Dehorter, N., Sols, I. et al. Lineage-specific laminar organization of cortical GABAergic interneurons. Nat Neurosci 16, 1199–1210 (2013) doi:10.1038/nn.3485
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