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[P49]: Inactivation of glycogen synthase kinase 3b links proliferation and self‐renewal of telencephalic neuroepithelial cells
Author(s) -
Shimizu T.,
Kagawa T.,
Inoue T.,
Yoshinaga Y.,
Takada S.,
Taga T.
Publication year - 2006
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2006.09.112
Subject(s) - gsk 3 , gsk3b , biology , kinase , biochemistry
Neural stem cells (NSCs) have the ability to self-renew and give rise to neurons, glia and oligodendrocytes; however, the signals that regulate NSCs are not well understood. In order to determine the role of -catenin in neural stem and progenitor cells of the mouse embryonic forebrain, we used Emx1-Cre and Nestin-Cre to restrict inactivation of a floxed β-catenin allele to neural precursor cells in the cerebral cortex and neuroepithelium, respectively. Emx1-Cre-mediated knockout of β-catenin is compatible with viability; however, null mice possess a significantly smaller cerebral cortex, defects in cortical lamination and loss of the hippocampus. Nestin-Cre-mediated knockout of β-catenin also leads to a smaller cerebral cortex and perinatal death. To determine how the neural precursor cell population is affected by loss of β-catenin, we performed an in vitro clonal neurosphere assay on E14.5 striatal germinal zone cells obtained from NestinCre/β-catenin-knockout embryos. Although β-catenin mutant cultures did not develop intact neurospheres, many individual cells were scattered throughout the cultures. This loss of cell adhesion seen in vitro may phenocopy the abnormal cortical morphogenesis that occurs in mutant mice in vivo. We also examined the self-renewal capacity of β-catenin mutant NSCs using a collagen-based, clonal colony forming assay. Although β-catenin mutant cells gave rise to smaller colonies than control cells, the total number of mutant colonies was significantly greater indicating the presence of more NSCs in the β-catenin mutant brain. These mutant colonies were passageable, demonstrating that -catenin is not required for NSC self-renewal. Furthermore, β-catenin mutant colonies retained multipotentiality as demonstrated by their ability to differentiate into neurons, astrocytes and oligodendrocytes. Therefore, we hypothesize that -catenin is required for proper adhesion of neural precursor cells via cadherins, and the proliferation of neural progenitor cells, but is not required for neural progenitor differentiation, and may act to inhibit the symmetric division of NSCs.