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Type 2 and type 3 inositol 1,4,5‐trisphosphate (IP 3 ) receptors promote the differentiation of granule cell precursors in the postnatal cerebellum
Author(s) -
Futatsugi Akira,
Ebisui Etsuko,
Mikoshiba Katsuhiko
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05221.x
Subject(s) - granule cell , cerebellum , microbiology and biotechnology , receptor , mutant , biology , inositol , granule (geology) , cellular differentiation , cell type , intracellular , cell , endocrinology , genetics , central nervous system , dentate gyrus , paleontology , gene
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 (IP 3 ) receptors (IP 3 R2 and IP 3 R3) 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 IP 3 R2 and IP 3 R3 did not affect the doubling time of GCPs. We conclude that intracellular calcium release via IP 3 R2s and IP 3 R3s promotes the differentiation of GCPs within a specific interval of postnatal development in the cerebellum.