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

• Main Authors: Christelle Cadilhac, Isabelle Bachy, Antoine Forget, David J. Hodson, Céline Jahannault-Talignani, Andrew J. Furley, Olivier Ayrault, Patrice Mollard, Constantino Sotelo, Fabrice Ango
• Format: Article
• Language: English
• Published: Elsevier 2021-03-01
• Series: Cell Reports
• Subjects: cerebellum; interneuron; tangential migration; GABA; cell type; stellate cell
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124721002187

Summary: 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.