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Publication : Glycoprotein 130 signaling regulates Notch1 expression and activation in the self-renewal of mammalian forebrain neural stem cells.

First Author  Chojnacki A Year  2003
Journal  J Neurosci Volume  23
Issue  5 Pages  1730-41
PubMed ID  12629177 Mgi Jnum  J:82269
Mgi Id  MGI:2651972 Doi  10.1523/JNEUROSCI.23-05-01730.2003
Citation  Chojnacki A, et al. (2003) Glycoprotein 130 signaling regulates Notch1 expression and activation in the self-renewal of mammalian forebrain neural stem cells. J Neurosci 23(5):1730-41
abstractText  Glycoprotein130 (gp130) and Notch signaling are thought to participate in neural stem cell (NSC) self-renewal. We asked whether gp130 regulates Notch activity in forebrain epidermal growth factor (EGF)-responsive NSCs. Disruption of Notch1 using antisense or a gamma-secretase inhibitor demonstrated a requirement for Notch1 in the maintenance and proliferation of NSCs. Ciliary neurotrophic factor (CNTF) activation of gp130 in NSCs rapidly increased Notch1 expression. NOTCH1 activation, indicated by tumor necrosis factor alpha-converting enzyme (TACE)- and presenilin-mediated processing, also increased. Infusion of EGF+CNTF into adult forebrain lateral ventricles increased periventricular NOTCH1 compared with EGF alone. Neither Hes1 (hairy and enhancer of split) nor Hes5 appeared to mediate gp130-enhanced NOTCH1 signaling that regulates NSC maintenance. This is the first example of a link between gp130 signaling and NOTCH1 in regulating NSC self-renewal.
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