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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 publication

DOI

10.1016/j.celrep.2021.108904

Type

Journal article

Journal

Cell Rep

Publication Date

2021

Volume

34

Keywords

Animals Axons/metabolism *Cell Differentiation Cell Movement Cytoplasmic Granules/*metabolism GABAergic Neurons/cytology Interneurons/*cytology/metabolism Mice, Transgenic *gaba *basket cell *cell type *cerebellum *interneuron *stellate cell *tangential migration