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Active intermixing of indirect and direct neurons builds the striatal mosaic

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posted on 08.02.2019, 10:17 by A Tinterri, F Menardy, M Diana, L Lokmane, M Keita, F Coulpier, S Lemoine, C Mailhes, B Mathieu, P Merchan-Sala, K Campbell, I Gyory, R Grosschedl, D Popa, S Garel
The striatum controls behaviors via the activity of direct and indirect pathway projection neurons (dSPN and iSPN) that are intermingled in all compartments. While such cellular mosaic ensures the balanced activity of the two pathways, its developmental origin and pattern remains largely unknown. Here, we show that both SPN populations are specified embryonically and intermix progressively through multidirectional iSPN migration. Using conditional mutant mice, we found that inactivation of the dSPN-specific transcription factor Ebf1 impairs selective dSPN properties, including axon pathfinding, while molecular and functional features of iSPN were preserved. Ebf1 mutation disrupted iSPN/dSPN intermixing, resulting in an uneven distribution. Such architectural defect was selective of the matrix compartment, highlighting that intermixing is a parallel process to compartment formation. Our study reveals while iSPN/dSPN specification is largely independent, their intermingling emerges from an active migration of iSPN, thereby providing a novel framework for the building of striatal architecture.


We are grateful to the IBENS Imaging Facility (France BioImaging, supported by ANR-10-INBS-04, ANR-10-LABX-54 MEMO LIFE and ANR-11-IDEX-000-02 PSL* Reseach University, “Investments for the future”; NERF N°2011-45; FRM DGE 20111123023; and FRC Rotary International France), the IBENS Genomics Facility (supported by the France Génomique national infrastructure, funded as part of the “Investissements d’Avenir” program managed by the Agence Nationale de la Recherche, ANR-10-INBS-09) and the IBENS acute transgenesis facility. A.T. is part of the ENP doctoral program. A.T. was supported by a doctoral fellowship from Boehringer Ingelheim Fonds (BIF), the ENP program and the Labex Memolife « Investements for the future » (ANR-10-LABX-54 MEMO LIFE and ANR-11-IDEX-0001-02 PSL* Research University). This work was supported by grants from INSERM, CNRS, the ANR program (ANR-12-BVS4-0010-01) and the ERC NImO (616080) to S.G, from the ANR program (ANR-12-JSV4-004) to D.P. and from NIH (R01 MH090740) to K.C.



Nature Communications, 2018, 9, Article number: 4725

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Supplementary Information accompanies this paper at https://doi.org/10.1038/s41467-018-07171-4



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