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Keywords:

  • calcium channels;
  • cerebellum;
  • development;
  • differentiation;
  • granule cell;
  • inositol 1,4,5-trisphosphate receptor

Abstract

During postnatal development of the cerebellum, granule cell precursors (GCPs) proliferate in the external granular layer (EGL), exit the cell cycle, differentiate, and migrate from the EGL to the internal granular layer. In the present study, we report that type 2 and 3 inositol 1,4,5-trisphosphate (IP3) receptors (IP3R2 and IP3R3) regulate the differentiation of GCPs after postnatal day 12 (P12). 5-Bromodeoxyuridine labeling experiments revealed that in mutant mice lacking both of these receptors (double mutants) a greater number of GCPs remain undifferentiated after P12. Consequently, the EGL of the double mutants is thicker than that of control mice at this age and thereafter. In addition, granule cells remain in the EGL of the double mutants at P21, an age when migration has concluded in wild-type mice. Whereas differentiation of GCPs was reduced in the double mutants, the absence of IP3R2 and IP3R3 did not affect the doubling time of GCPs. We conclude that intracellular calcium release via IP3R2s and IP3R3s promotes the differentiation of GCPs within a specific interval of postnatal development in the cerebellum.