Pax-2 expression defines a subset of GABAergic interneurons and their precursors in the developing murine cerebellum

Pax-2 is a paired box transcription factor expressed in several regions of the developing mammalian central nervous system. First found in the midbrai n/hindbrain region, Pax-2 expression is later found in the cerebellum, hind brain, and spinal cord. We have examined the expression pattern of Pax-2 fr om embryonic day 12 (E12) through postnatal day 35 (P35) using immunohistoc hemistry and in situ hybridization, Expression of Pax-2 is found in scatter ed cells of the cerebellar ventricular zone at E13, Pax-2-expressing cells migrate away from this germinative center to positions in the deep cerebell ar nuclei (DCN), internal granule cell layer, molecular layer, and folial w hite-matter tracts of the cerebellum, Immunocytochemistry of both tissue se ctions and primary dissociated cultures demonstrates that Pax-2 is expresse d by cells of a neuronal lineage, but not by cells of either an astrocytic or oligodendrocytic lineage. Specifically, the presence of Pax-2 identifies the entire population of gamma-aminobutyric acid (GABA)ergic interneurons in the cerebellar cortex (Golgi II, basket and stellate cells) and in the D CN, Bromodeoxyuridase labeling and 4',6-diamino-2-phenylindole (DAPI) stain ing of cells in M-phase reveals that Pax-2-expressing cells in the folial w hite-matter tracts of the cerebellum constitute an actively dividing popula tion. We propose that these cells are migratory precursors of the molecular layer interneurons (basket and stellate cells). Our data suggest that the role of Pax-2 in cerebellar development changes after E12, shifting from th e specification of an anatomical field to the marking of a specific class o f cells, Our findings also suggest a previously uncharacterized relationshi p among GABAergic interneurons found posterior to the midbrain. Finally, ou r data support the hypothesis that the basket and stellate cells arise from neuronally restricted, migratory precursors located in the early postnatal cerebellar white matter. (C) 1999 John Wiley & Sons, Inc.