Format

Send to

Choose Destination
Nat Commun. 2018 Nov 9;9(1):4725. doi: 10.1038/s41467-018-07171-4.

Active intermixing of indirect and direct neurons builds the striatal mosaic.

Author information

1
Brain Development and Plasticity Team, Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Université Paris, 75005, Paris, France.
2
Boehringer Ingelheim Fonds, Foundation for Basic Research in Medicine, Schusterstr. 46-48, 55116, Mainz, Germany.
3
Ecole de Neurosciences de Paris Ile de France, 15 rue de l'Ecole de Medicine, 75006, Paris, France.
4
Neurophysiology of Brain Circuits Team, Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Université Paris, 75005, Paris, France.
5
UPMC University Paris 06, UM119 Neuroscience Paris Seine (NPS), CNRS UMR8246, Inserm, U1130, Paris, France.
6
Genomics Facility, Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Université Paris, 75005, Paris, France.
7
Acute Transgenesis Facility, Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Université Paris, 75005, Paris, France.
8
Photon Microscopy Facility, Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Université Paris, 75005, Paris, France.
9
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
10
Department of Cellular and Molecular Immunology, Max Plank Institute of Immunobiology, Stuebeweg 51, 79108, Freiburg, Germany.
11
Brain Development and Plasticity Team, Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Université Paris, 75005, Paris, France. garel@biologie.ens.fr.

Abstract

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center