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The Journal of Neuroscience, March 1, 2003, 23(5):1730

Glycoprotein 130 Signaling Regulates Notch1 Expression and Activation in the Self-Renewal of Mammalian Forebrain Neural Stem Cells

Andrew Chojnacki¹, Takuya Shimazaki¹, Christopher Gregg¹, Gerry Weinmaster², and Samuel Weiss¹

¹ Genes & Development Research Group, Department of Cell Biology and Anatomy, University of Calgary, Faculty of Medicine, Calgary, Alberta, Canada T2N 4N1, and ² Department of Biological Chemistry, Molecular Biology Institute, University of California at Los Angeles School of Medicine, Los Angeles, California 90095-1737

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 -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 -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.

Key words: notch; gp130; CNTF; stem cell; delta; self-renewal

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Copyright © 2003 Society for Neuroscience  0270-6474/03/2351730-12$05.00/0

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