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

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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 languageEnglish
Article number108904
JournalCell Reports
Volume34
Issue number13
Early online date30 Mar 2021
DOIs
Publication statusE-pub ahead of print - 30 Mar 2021

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