NB-3/Notch1 pathway via Deltex1 promotes neural progenitor cell differentiation into oligodendrocytes.
Neurons and glia in the vertebrate central nervous system arise in temporally distinct, albeit overlapping, phases. Neurons are generated first followed by astrocytes and oligodendrocytes from common progenitor cells. Increasing evidence indicates that axon-derived signals spatiotemporally modulate oligodendrocyte maturation and myelin formation. Our previous observations demonstrate that F3/contactin is a functional ligand of Notch during oligodendrocyte maturation, revealing the existence of another group of Notch ligands. Here, we establish that NB-3, a member of the F3/contactin family, acts as a novel Notch ligand to participate in oligodendrocyte generation. NB-3 triggers nuclear translocation of the Notch intracellular domain and promotes oligodendrogliogenesis from progenitor cells and differentiation of oligodendrocyte precursor cells via Deltex1. In primary oligodendrocytes, NB-3 increases myelin-associated glycoprotein transcripts. Thus, the NB-3/Notch signaling pathway may prove to be a molecular handle to treat demyelinating diseases.
Cui
Xiao-Ying
XY
Department of Clinical Research and Group of Stem Cell Research, Singapore General Hospital, Singapore 169608.
Hu
Qi-Dong
QD
Tekaya
Meriem
M
Shimoda
Yasushi
Y
Ang
Beng-Ti
BT
Nie
Du-Yu
DY
Sun
Li
L
Hu
Wei-Ping
WP
Karsak
Meliha
M
Duka
Tanya
T
Takeda
Yasuo
Y
Ou
Lian-Yun
LY
Dawe
Gavin S
GS
Yu
Feng-Gang
FG
Ahmed
Sohail
S
Jin
Lian-Hong
LH
Schachner
Melitta
M
Watanabe
Kazutada
K
Arsenijevic
Yvan
Y
Xiao
Zhi-Cheng
ZC
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D015816:Cell Adhesion Molecules, Neuronal / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D058966:Contactins; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000166:cytology*; D009836:Oligodendroglia / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors
D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; C104189:Cntn6 protein, rat; D058966:Contactins; C497762:Notch1 protein, mouse; C497763:Notch1 protein, rat; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors; C409218:deltex protein, vertebrate