Notch targets the Cdk inhibitor Xic1 to regulate differentiation but not the cell cycle in neurons.

EMBO Reports
Ann E VernonAnna Philpott

Abstract

The proneural protein neurogenin (XNGNR1) drives differentiation of primary neurons in combination with the cyclin-dependent kinase (Cdk) inhibitor Xic1. Differentiation is inhibited by Notch signalling, resulting in a scattered neuronal distribution. Here we show that Notch signalling regulates the level of Xic1 transcription, yet this does not correlate with Notch's ability to perturb the cell cycle. Instead, Notch may regulate Xic1 levels to control its differentiation function directly, which is required in parallel with XNGNR1 to promote primary neurogenesis. Indeed, Notch-mediated repression of both XNGNR1 and Xic1 must be relieved for neuronal differentiation to occur. Interestingly, although Xic1 is required for XNGNR1-mediated neurogenesis, it is not required for XNGNR1-mediated upregulation of Delta, allowing establishment of the negative feedback loop involved in lateral inhibition. Therefore, Notch targets Cdk inhibitor expression to regulate differentiation of primary neurons, and its effects on the cell cycle may be of secondary importance.

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Citations

Feb 13, 2008·Molecular Biotechnology·Anna Philpott, P Renee Yew
Dec 18, 2007·Neural Development·Hector Boix-PeralesAnna Philpott
Dec 11, 2008·Neurochemical Research·Jyotshnabala KanungoHarish C Pant
Feb 24, 2015·Developmental Biology·Laura J A Hardwick, Anna Philpott
Jan 29, 2010·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Aikaterini Bilitou, Shin-ichi Ohnuma
Mar 1, 2012·Developmental Biology·Antonella BizzocaGianfranco Gennarini
Mar 4, 2008·Nature Cell Biology·Mark P Mattson, Henriette van Praag
May 31, 2012·The Biochemical Journal·Christopher Hindley, Anna Philpott
Apr 29, 2020·Cancer Research·Seyedeh Fatemeh RazavipourJoyce M Slingerland
Feb 10, 2018·Journal of Molecular Biology·Gustavo Martínez-NoëlPeter M Howley

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