Excitatory granule neuron precursors orchestrate laminar localization and differentiation of cerebellar inhibitory interneuron subtype
Research output: Contribution to journal › Article › peer-review
Colleges, School and Institutes
GABAergic interneurons migrate long distances through stereotyped migration programs toward specific laminar positions. During their migration, GABAergic interneurons are morphologically alike but then differentiate into a rich array of interneuron subtypes critical for brain function. How interneuron subtypes acquire their final phenotypic traits remains largely unknown. Here, we show that cerebellar molecular layer GABAergic interneurons, derived from the same progenitor pool, use separate migration paths to reach their laminar position and differentiate into distinct basket cell (BC) and stellate cell (SC) GABAergic interneuron subtypes. Using two-photon live imaging, we find that SC final laminar position requires an extra step of tangential migration supported by a subpopulation of glutamatergic granule cells (GCs). Conditional depletion of GCs affects SC differentiation but does not affect BCs. Our results reveal how timely feedforward control of inhibitory interneuron migration path regulates their terminal differentiation and, thus, establishment of the local inhibitory circuit assembly.
Funding information: This work was supported by ANR-14-CE12-0015-03 and ERA-Net NEURON/DECODE (18-NEUR-0004) to F.A. D.J.H. was supported by MRC (MR/N00275X/1 and MR/S025618/1) and Diabetes UK (17/0005681) project grants. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (starting grant 715884 to D.J.H.). P.M. was supported by the Agence Nationale de la Recherche (ANR-15-CE14-0012-01 and ANR-18-CE14-0017-01) and France-Bioimaging (INBS10-GaL/AR-11/12). C.C. was supported by a fellowship from the French Ministry of Research and Education. We thank Pierre Fontanaud for his help in initial video tracking analysis and the iExplore and RIO-Imaging Platforms of the IGF for their support. We also thank IGF direction and J.P. Pin for their support of this project.
|Early online date||30 Mar 2021|
|Publication status||E-pub ahead of print - 30 Mar 2021|