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Mariona Arbones: Proliferation and differentiation of the nervous system

Lab Presentation

The group studies the cellular and molecular mechanisms that control growth and cell diversity in the mammalian central nervous system. We are particularly interested in the neocortex, the brain region involved in higher cognitive functions. The many type of neurons that form an adult neocortex are generated prenatally from progenitor types located in different germinal regions. We aim to uncover intrinsic and extrinsic factors that are important for the proliferation and differentiation of these progenitors. We are also interested in understanding the pathogenic mechanisms that are responsible for the cerebral cortical alterations associated to Down syndrome and to a particular type of autism spectrum disorder caused by mutations in DYRK1A. Our experimental approach includes morphological and functional studies in mice that model these disorders, as well as proteomics and high-throughput sequencing techniques.

Mariona Arbonés Rafael

Principal Investigator

Past students

  • Sonia Najas

    Postdoctoral Researcher


Najas S, Arranz J, Lochhead PA, Ashford AL, Oxley D, Delabar JM, Cook SJ, Barallobre MJ, Arbonés ML. DYRK1A-mediated Cyclin D1 Degradation in Neural Stem Cells Contributes to the Neurogenic Cortical Defects in Down Syndrome. EBioMedicine 2015. 2(2):120-34.

Blazek JD, Malik AM, Tischbein M, Arbones ML, Moore CS, Roper RJ. Abnormal mineralization of the Ts65Dn Down syndrome mouse appendicular skeleton begins during embryonic development in a Dyrk1a-independent manner. Mech Dev 2015. 136:133-42.

García-Cerro S, Martínez P, Vidal V, Corrales A, Flórez J, Vidal R, Rueda N, Arbonés ML, Martínez-Cué C. Overexpression of Dyrk1A is implicated in several cognitive, electrophysiological and neuromorphological alterations found in a mouse model of Down syndrome. PLoS One 2014. 9(9):e106572.

Janel N, Sarazin M, Corlier F, Corne H, de Souza LC, Hamelin L, Aka A, Lagarde J, Blehaut H, Hindié V, Rain JC, Arbones ML, Dubois B, Potier MC, Bottlaender M, Delabar JM. Plasma DYRK1A as a novel risk factor for Alzheimer's disease. Transl Psychiatry , 2014. 4:e425.

Barallobre MJ, Perier C, Bové J, Laguna A, Delabar JM, Vila M, Arbonés ML. DYRK1A promotes dopaminergic neuron survival in the developing brain and in a mouse model of Parkinson's disease. Cell Death Dis 2014. 5:e1289.

Souchet B, Guedj F, Sahún I, Duchon A, Daubigney F, Badel A, Yanagawa Y, Barallobre MJ, Dierssen M, Yu E, Herault Y, Arbones M, Janel N, Créau N, Delabar JM. Excitation/inhibition balance and learning are modified by Dyrk1a gene dosage. Neurobiol Dis 2014. 69:65-75.

Rachdi L, Kariyawasam D, Guez F, Aïello V, Arbonés ML, Janel N, Delabar JM, Polak M, Scharfmann R. Dyrk1a haploinsufficiency induces diabetes in mice through decreased pancreatic beta cell mass. Diabetologia 2014. 57(5):960-9

Martin KR, Layton D, Seach N, Corlett A, Barallobre MJ, Arbonés ML, Boyd RL, Scott B, Pritchard MA. Upregulation of RCAN1 causes Down syndrome-like immune dysfunction. J Med Genet 2013. 50(7):444-54.

Laguna A, Barallobre MJ, Marchena MÁ, Mateus C, Ramírez E, Martínez-Cue C, Delabar JM, Castelo-Branco M, de la Villa P, Arbonés ML. Triplication of DYRK1A causes retinal structural and functional alterations in Down syndrome. Hum Mol Genet 2013. 22(14):2775-84.

Martin KR, Corlett A, Dubach D, Mustafa T, Coleman HA, Parkington HC, Merson TD, Bourne JA, Porta S, Arbonés ML, Finkelstein DI, Pritchard MA. Over-expression of RCAN1 causes Down syndrome-like hippocampal deficits that alter learning and memory. Hum Mol Genet 2012. 21(13):3025-4, 2012.

Sobrado M, Ramirez BG, Neria F, Lizasoain I, Arbones ML, Minami T, Redondo JM, Moro MA, Cano E. Regulator of calcineurin 1 (Rcan1) has a protective role in brain ischemia/reperfusion injury. J Neuroinflammation 2012. 9:48.

Guedj F, Pereira PL, Najas S, Barallobre MJ, Chabert C, Souchet B, Sebrie C, Verney C, Herault Y, Arbones M, Delabar JM. DYRK1A: a master regulatory protein controlling brain growth. Neurobiol Dis 2012. 46(1):190-203.

Oeschger FM, Wang WZ, Lee S, García-Moreno F, Goffinet AM, Arbonés ML, Rakic S, Molnár Z. Gene expression analysis of the embryonic subplate. Cereb Cortex 2012. 22(6):1343-59.

Esteban V, Méndez-Barbero N, Jiménez-Borreguero LJ, Roqué M, Novensá L, García-Redondo AB, Salaices M, Vila L, Arbonés ML, Campanero MR, Redondo JM. Regulator of calcineurin 1 mediates pathological vascular wall remodeling. J Exp Med 2011. 208(10):2125-39.

da Costa Martins PA, Salic K, Gladka MM, Armand AS, Leptidis S, el Azzouzi H, Hansen A, Coenen-de Roo CJ, Bierhuizen MF, van der Nagel R, van Kuik J, de Weger R, de Bruin A, Condorelli G, Arbones ML, Eschenhagen T, De Windt LJ. MicroRNA-199b targets the nuclear kinase Dyrk1a in an auto-amplification loop promoting calcineurin/NFAT signalling. Nat Cell Biol 2010. 12(12):1220-7.

Arqué G, de Lagrán MM, Arbonés ML, Dierssen M. Age-associated motor and visuo-spatial learning phenotype in Dyrk1A heterozygous mutant mice. Neurobiol Dis 2009. 36(2):312-9.

Guedj F, Sébrié C, Rivals I, Ledru A, Paly E, Bizot JC, Smith D, Rubin E, Gillet B, Arbones M, Delabar JM. Green tea polyphenols rescue of brain defects induced by overexpression of DYRK1A. PLoS One 2009. 4(2):e4606.

Ferron SR, Pozo N, Laguna A, Aranda S, Porlan E, Moreno M, Fillat C, de la Luna S, Sánchez P, Arbonés ML*, Fariñas I*. Regulated segregation of kinase Dyrk1A during asymmetric neural stem cell division is critical for EGFR-mediated biased signaling. Cell Stem Cell. 7(3):367-79, 2010.

Laguna A, Aranda S, Barallobre MJ, Barhoum R, Fernández E, Fotaki V, Delabar JM, de la Luna S, de la Villa P, Arbonés ML. The protein kinase DYRK1A regulates caspase-9-mediated apoptosis during retina development. Dev Cell 2008. 15(6):841-53.

Arqué G, Fotaki V, Fernández D, Martínez de Lagrán M, Arbonés ML, Dierssen M. Impaired spatial learning strategies and novel object recognition in mice haploinsufficient for the dual specificity tyrosine-regulated kinase-1A (Dyrk1A). PLoS One 2008. 3(7):e2575.

Ballana E, Wang J, Venail F, Estivill X, Puel JL, Arbonès ML, Bosch A. Efficient and specific transduction of cochlear supporting cells by adeno-associated virus serotype 5. Neurosci Lett 2008. 442(2):134-9.

Keating DJ, Dubach D, Zanin MP, Yu Y, Martin K, Zhao YF, Chen C, Porta S, Arbonés ML, Mittaz L, Pritchard MA. DSCR1/RCAN1 regulates vesicle exocytosis and fusion pore kinetics: implications for Down syndrome and Alzheimer's disease. Hum Mol Genet 2008 17(7):1020-30.

Porta S, Martí E, de la Luna S, Arbonés ML. Differential expression of members of the RCAN family of calcineurin regulators suggests selective functions for these proteins in the brain. Eur J Neurosci 2007. 26(5):1213-26.

Porta S, Serra SA, Huch M, Valverde MA, Llorens F, Estivill X, Arbonés ML, Martí E. RCAN1 (DSCR1) increases neuronal susceptibility to oxidative stress: a potential pathogenic process in neurodegeneration. Hum Mol Genet 2007. 16(9):1039-50.

Martinez de Lagran M, Bortolozzi A, Millan O, Gispert JD, Gonzalez JR, Arbones ML, Artigas F, Dierssen M. Dopaminergic deficiency in mice with reduced levels of the dual-specificity tyrosine-phosphorylated and regulated kinase 1A, Dyrk1A(+/-). Genes Brain Behav 2007. 6(6):569-78.

Venail F, Wang J, Ruel J, Ballana E, Rebillard G, Eybalin M, Arbones M, Bosch A, Puel JL. Coxsackie adenovirus receptor and alpha nu beta3/alpha nu beta5 integrins in adenovirus gene transfer of rat cochlea. Gene Ther 2007. 14(1):30-7. 

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