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

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. [Display omitted] •Basket cells and stellate cells use stereotyped migration paths in cerebellum•Stellate cells migrate tangentially in the external granule cell layer•Immature granule cell neurites support stellate cell tangential migration•Genetic depletion of granule cells affects stellate cell differentiation Cadilhac et al. report that molecular layer GABAergic progenitors use distinct migration paths to reach their laminar position in the cerebellum where they differentiate into basket cells (BCs) and stellate cells (SCs). SCs perform an additional tangential migration step along immature granule cell neurites whose genetic depletion mainly affects SC differentiation.