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 midbrain/hindbrain region, Pax-2 expression is later found in the cerebellum, hindbrain, and spinal cord. We have examined the expression pattern of Pax-2 from embryonic day 12 (E12) through postnatal day 35 (P35) using immunohistochemistry and in situ hybridization. Expression of Pax-2 is found in scattered cells of the cerebellar ventricular zone at E13. Pax-2-expressing cells migrate away from this germinative center to positions in the deep cerebellar nuclei (DCN), internal granule cell layer, molecular layer, and folial white-matter tracts of the cerebellum. Immunocytochemistry of both tissue sections and primary dissociated cultures demonstrates that Pax-2 is expressed 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 DCN. Bromodeoxyuridase labeling and 4',6-diamino-2-phenylindole (DAPI) staining of cells in M-phase reveals that Pax-2-expressing cells in the folial white-matter tracts of the cerebellum constitute an actively dividing population. 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 the specification of an anatomical field to the marking of a specific class of cells. Our findings also suggest a previously uncharacterized relationship among GABAergic interneurons found posterior to the midbrain. Finally, our data support the hypothesis that the basket and stellate cells arise from neuronally restricted, migratory precursors located in the early postnatal cerebellar white matter.
Maricich
S M
SM
Alzheimer Research Laboratory, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA.
Herrup
K
K
D000818:Animals; D015415:Biomarkers; D002451:Cell Compartmentation / Q000502:physiology; D048429:Cell Size / Q000502:physiology; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology / Q000196:embryology; D002529:Cerebellar Nuclei / Q000166:cytology / Q000196:embryology*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D007395:Interneurons / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis / Q000502:physiology; D051762:PAX2 Transcription Factor; D012333:RNA, Messenger / Q000032:analysis; D013234:Stem Cells / Q000737:chemistry / Q000502:physiology*; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D015415:Biomarkers; D004268:DNA-Binding Proteins; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D005680:gamma-Aminobutyric Acid