Group III metabotropic glutamate receptor activation suppresses self-replication of undifferentiated neocortical progenitor cells.
We evaluated the possible functional expression of metabotropic glutamate receptors (mGluRs) by neural progenitors from embryonic mouse neocortex. Constitutive expression was seen with group I, II, and III mGluRs in undifferentiated cells and neurospheres formed by clustered cells during culture with epidermal growth factor. The group III mGluR agonist, L-2-amino-4-phosphonobutyrate, drastically reduced proliferation activity at 1-100 microM without inducing cell death, with group I and group II mGluR agonists being ineffective, in these neurospheres. Both forskolin and a group III mGluR antagonist significantly increased the proliferation alone, but significantly prevented the suppression by L-2-amino-4-phosphonobutyrate. Activation of group III mGluR significantly decreased mRNA expression of the cell cycle regulator cyclinD1, in addition to inhibiting the transactivation mediated by cAMP of cyclinD1 gene in the pluripotent P19 progenitor cells. Prior activation of group III mGluR led to a significant decrease in the number of cells immunoreactive for a neuronal marker, with an increase in that for an astroglial marker irrespective of differentiation inducers. These results suggest that group III mGluR may be functionally expressed to suppress self-renewal capacity through a mechanism related to cAMP formation with promotion of subsequent differentiation into astroglial lineage in neural progenitors.
Nakamichi
Noritaka
N
Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology, Kanazawa, Ishikawa, Japan.
Yoshida
Kohei
K
Ishioka
Yukichi
Y
Makanga
Juliet O
JO
Fukui
Masaki
M
Yoneyama
Masanori
M
Kitayama
Tomoya
T
Nakamura
Nobuhiro
N
Taniura
Hideo
H
Yoneda
Yukio
Y
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006131:Growth Inhibitors / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D019579:Neocortex / Q000166:cytology / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism* / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
D006131:Growth Inhibitors; D018094:Receptors, Metabotropic Glutamate; C102718:metabotropic glutamate receptor 3