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.
References
Oct 24, 1995·Proceedings of the National Academy of Sciences of the United States of America·J Y SuJ L Maller
Jun 29, 1995·Nature·A ChitnisC Kintner
May 12, 1995·Science·J E LeeH Weintraub
May 21, 1993·Cell·C R CoffmanC R Kintner
Oct 4, 1996·Cell·Q MaD J Anderson
Dec 27, 1996·Cell·E J BellefroidT Pieler
Jul 27, 2000·Molecular and Cellular Biology·P CastellaM Caudy
Jan 11, 2001·Developmental Biology·Y Saka, J C Smith
Jul 4, 2001·The EMBO Journal·A RangarajanG P Dotto
Sep 8, 2001·Neuron·D J SoleckiM E Hatten
Apr 10, 2002·Molecular and Cellular Biology·Virote SriuranpongDouglas W Ball
Nov 21, 2002·Development·Ann E VernonAnna Philpott
Feb 1, 2003·Trends in Cell Biology·Olivier Coqueret
Jun 1, 2005·Experimental Cell Research·Ryoichiro KageyamaRyosuke Ohsawa
Jul 7, 2005·The Journal of Experimental Medicine·Leonor M SarmentoNadia Carlesso
Aug 2, 2005·Nature Cell Biology·Tarig Bashir, Michele Pagano
Citations
Feb 13, 2008·Molecular Biotechnology·Anna Philpott, P Renee Yew
Dec 18, 2007·Neural Development·Hector Boix-PeralesAnna Philpott
Nov 3, 2010·PloS One·Sergey V Prykhozhij
Feb 1, 2012·Stem Cell Reviews and Reports·Simone HauptFrank Edenhofer
Dec 11, 2008·Neurochemical Research·Jyotshnabala KanungoHarish C Pant
Feb 24, 2015·Developmental Biology·Laura J A Hardwick, Anna Philpott
Jan 9, 2013·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Takeshi KawauchiYoichi Kosodo
Nov 15, 2011·Developmental Neurobiology·Anna TuryEmanuel DiCicco-Bloom
Mar 18, 2010·Stem Cells·Lodovica BorgheseOliver Brüstle
Jan 29, 2010·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Aikaterini Bilitou, Shin-ichi Ohnuma
Sep 14, 2010·Developmental Cell·Lidia HernandezColin L Stewart
Mar 1, 2012·Developmental Biology·Antonella BizzocaGianfranco Gennarini
Mar 4, 2008·Nature Cell Biology·Mark P Mattson, Henriette van Praag
Apr 12, 2011·Cell Cycle·Cristina MenchónJuan Carlos Izpisua Belmonte
May 31, 2012·The Biochemical Journal·Christopher Hindley, Anna Philpott
Jan 1, 2015·Neurogenesis·Anna Philpott
Dec 22, 2009·Oncogene·K MasudaK Nakayama
Aug 17, 2012·Cell Cycle·Yuji Tsunekawa, Noriko Osumi
Apr 29, 2020·Cancer Research·Seyedeh Fatemeh RazavipourJoyce M Slingerland
Feb 10, 2018·Journal of Molecular Biology·Gustavo Martínez-NoëlPeter M Howley