Increased dosage of DYRK1A and DSCR1 delays neuronal differentiation in neocortical progenitor cells

Genes & Development
Nobuhiro Kurabayashi, Kamon Sanada

Abstract

Down's syndrome (DS), a major genetic cause of mental retardation, arises from triplication of genes on human chromosome 21. Here we show that DYRK1A (dual-specificity tyrosine-phosphorylated and -regulated kinase 1A) and DSCR1 (DS critical region 1), two genes lying within human chromosome 21 and encoding for a serine/threonine kinase and calcineurin regulator, respectively, are expressed in neural progenitors in the mouse developing neocortex. Increasing the dosage of both proteins in neural progenitors leads to a delay in neuronal differentiation, resulting ultimately in alteration of their laminar fate. This defect is mediated by the cooperative actions of DYRK1A and DSCR1 in suppressing the activity of the transcription factor NFATc. In Ts1Cje mice, a DS mouse model, dysregulation of NFATc in conjunction with increased levels of DYRK1A and DSCR1 was observed. Furthermore, counteracting the dysregulated pathway ameliorates the delayed neuronal differentiation observed in Ts1Cje mice. In sum, our findings suggest that dosage of DYRK1A and DSCR1 is critical for proper neurogenesis through NFATc and provide a potential mechanism to explain the neurodevelopmental defects in DS.

References

Jan 1, 1993·European Journal of Human Genetics : EJHG·J M DelabarP M Sinet
Sep 1, 1994·Journal of Neuropathology and Experimental Neurology·J A Golden, B T Hyman
Jan 1, 1996·Nature Medicine·R E Tanzi
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·H SagoT T Huang
Feb 18, 1999·Molecular and Cellular Biology·C W ChowR J Davis
Jul 19, 2000·Mental Retardation and Developmental Disabilities Research Reviews·R S Chapman, L J Hesketh
Apr 18, 2002·Proceedings of the National Academy of Sciences of the United States of America·Guangchao SuiYang Shi
Aug 23, 2002·Molecular and Cellular Biology·Vassiliki FotakiMaria L Arbonés
Sep 13, 2002·The Journal of Biological Chemistry·Eva van RooijLeon J de Windt
Apr 18, 2003·Lancet·Nancy J Roizen, David Patterson
Sep 29, 2004·The Journal of Comparative Neurology·Marta NietoChristopher A Walsh
Oct 29, 2004·Nature Reviews. Genetics·Stylianos E AntonarakisSamuel Deutsch
Mar 24, 2006·Nature·Joseph R ArronGerald R Crabtree
Oct 20, 2006·Birth Defects Research. Part A, Clinical and Molecular Teratology·Mark A CanfieldRussell S Kirby
Oct 26, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Lina ChakrabartiTarik F Haydar
Oct 26, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Naoyuki AsadaYoshitaka Fukada
Dec 21, 2007·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Tuan Nguyen, Simone Di Giovanni
Mar 20, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Odessa YabutGabriella D'Arcangelo
Aug 21, 2010·Nature Reviews. Immunology·Martin R Müller, Anjana Rao
Feb 2, 2012·Neurobiology of Disease·Fayçal GuedjJean M Delabar

❮ Previous
Next ❯

Citations

Apr 18, 2015·Neural Regeneration Research·Michael Telias, Dalit Ben-Yosef
Mar 24, 2015·Nutrition Research·Peter A ZmijewskiDana R Crawford
Nov 29, 2017·Stem Cells and Development·Hedwig S KruitwagenBart Spee
Mar 11, 2018·Scientific Reports·Bradley PawlikowskiBradley B Olwin
Dec 21, 2014·The EMBO Journal·Benedetta ArtegianiFederico Calegari
Sep 11, 2019·FEBS Letters·Saishu Yoshida, Kiyotsugu Yoshida
Dec 11, 2019·Cells·Laura ReichePeter Göttle
Dec 14, 2016·PeerJ·Vanja DakicStevens K Rehen
Feb 15, 2019·Laboratory Investigation; a Journal of Technical Methods and Pathology·Momoko InoueAkihiro Umezawa
Sep 24, 2020·International Journal of Molecular Sciences·Carmen Martínez-Cué, Noemí Rueda
Jul 5, 2017·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Nobuhiro Kurabayashi, Kamon Sanada
Oct 1, 2018·Pharmacology & Therapeutics·Maria L ArbonesJean M Delabar
May 1, 2021·International Journal of Molecular Sciences·Brianna ChenAriadna Recasens
Sep 23, 2021·Journal of Plant Research·Tomoyuki FuruyaHirokazu Tsukaya

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.