Disruption of CK2beta in embryonic neural stem cells compromises proliferation and oligodendrogenesis in the mouse telencephalon.
Genetic programs that govern neural stem/progenitor cell (NSC) proliferation and differentiation are dependent on extracellular cues and a network of transcription factors, which can be regulated posttranslationally by phosphorylation. However, little is known about the kinase-dependent pathways regulating NSC maintenance and oligodendrocyte development. We used a conditional knockout approach to target the murine regulatory subunit (beta) of protein kinase casein kinase 2 (CK2beta) in embryonic neural progenitors. Loss of CK2beta leads to defects in proliferation and differentiation of embryonic NSCs. We establish CK2beta as a key positive regulator for the development of oligodendrocyte precursor cells (OPCs), both in vivo and in vitro. We show that CK2beta directly interacts with the basic helix-loop-helix (bHLH) transcription factor Olig2, a critical modulator of OPC development, and activates the CK2-dependent phosphorylation of its serine-threonine-rich (STR) domain. Finally, we reveal that the CK2-targeted STR domain is required for the oligodendroglial function of Olig2. These findings suggest that CK2 may control oligodendrogenesis, in part, by regulating the activity of the lineage-specific transcription factor Olig2. Thus, CK2beta appears to play an essential and uncompensated role in central nervous system development.
Huillard
Emmanuelle
E
INSERM, U873, CEA, iRTSV/LTS, 17 Av. des Martyrs, F-38054 Grenoble, France.
Ziercher
Léa
L
Blond
Olivier
O
Wong
Michael
M
Deloulme
Jean-Christophe
JC
Souchelnytskyi
Serhiy
S
Baudier
Jacques
J
Cochet
Claude
C
Buchou
Thierry
T
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000033:anatomy & histology / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013687:Telencephalon / Q000002:abnormalities / Q000166:cytology / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D047390:Casein Kinase II; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; C512773:Olig2 protein, mouse