Excitatory granule neuron precursors orchestrate laminar localization and differentiation of cerebellar inhibitory interneuron subtype

Christelle Cadilhac; Isabelle Bachy; Antoine Foget; David Hodson; Celine Jahannault-Talignani; Andrew  Furley; Olivier Ayrault; Patrice Mollard; Constantino Sotelo; Fabrice  Ango

doi:10.1016/j.celrep.2021.108904

Excitatory granule neuron precursors orchestrate laminar localization and differentiation of cerebellar inhibitory interneuron subtype

Christelle Cadilhac, Isabelle Bachy, Antoine Foget, David Hodson, Celine Jahannault-Talignani, Andrew Furley, Olivier Ayrault, Patrice Mollard, Constantino Sotelo, Fabrice Ango

Metabolism and Systems Research

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Abstract

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.

Original language	English
Article number	108904
Journal	Cell Reports
Volume	34
Issue number	13
Early online date	30 Mar 2021
DOIs	https://doi.org/10.1016/j.celrep.2021.108904
Publication status	E-pub ahead of print - 30 Mar 2021

Bibliographical note

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.

Keywords

GABA
basket cell
cell type
cerebellum
interneuron
stellate cell
tangential migration

ASJC Scopus subject areas

General Biochemistry,Genetics and Molecular Biology

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CadilhacC2021ExcitatoryFinal published version, 14.9 MBLicence: Creative Commons: Attribution-NonCommercial-NoDerivs (CC BY-NC-ND)

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Cadilhac, C., Bachy, I., Foget, A., Hodson, D., Jahannault-Talignani, C., Furley, A., Ayrault, O., Mollard, P., Sotelo, C., & Ango, F. (2021). Excitatory granule neuron precursors orchestrate laminar localization and differentiation of cerebellar inhibitory interneuron subtype. Cell Reports, 34(13), Article 108904. Advance online publication. https://doi.org/10.1016/j.celrep.2021.108904

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abstract = "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.",

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author = "Christelle Cadilhac and Isabelle Bachy and Antoine Foget and David Hodson and Celine Jahannault-Talignani and Andrew Furley and Olivier Ayrault and Patrice Mollard and Constantino Sotelo and Fabrice Ango",

note = "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{\textquoteright}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.",

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AU - Hodson, David

AU - Jahannault-Talignani, Celine

AU - Furley, Andrew

AU - Ayrault, Olivier

AU - Mollard, Patrice

AU - Sotelo, Constantino

AU - Ango, Fabrice

N1 - 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.

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N2 - 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.

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Excitatory granule neuron precursors orchestrate laminar localization and differentiation of cerebellar inhibitory interneuron subtype

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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