Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-018-07171-4
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Funding
- NERF [2011-45]
- FRM [DGE 20111123023]
- FRC Rotary International France
- France Genomique national infrastructure as part of the Investissements d'Avenir program [ANR-10-INBS-09]
- Boehringer Ingelheim Fonds (BIF)
- ENP program
- Labex Memolife Investements for the future [ANR-10-LABX-54 MEMO LIFE, ANR-11-IDEX-0001-02]
- INSERM
- CNRS
- ANR program [ANR-12-BVS4-0010-01, ANR-12-JSV4-004]
- ERC NImO [616080]
- NIH [R01 MH090740]
- [ANR-10-INBS-04]
- European Research Council (ERC) [616080] Funding Source: European Research Council (ERC)
- MRC [MR/L001152/1] Funding Source: UKRI
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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.
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