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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 the neocortex are generated prenatally from different progenitor sets located in specific germinal domains. We aim to uncover intrinsic factors and extracellular cues that are relevant for the correct proliferation and differentiation of these progenitors during neurogenesis. We are also interested in understanding the pathogenic mechanisms underlying autism, intellectual disability and other neurodevelopmental disorders. An important effort of the group has been the study of DYRK1A, a dosage-sensitive kinase involved in Down syndrome and in DYRK1A haploinsufficiency syndrome, in neural proliferation, differentiation and survival.

Our experimental approach includes morphological and functional studies in mutant mice and molecular studies in cell cultures.

Projects

  • DYRK1A in neural proliferation and neuronal differentiation
  • Extracellular matrix in the developing cerebral cortex

Lab people

Principal investigator

Mariona Arbonés graduated in Biological Sciences at the Autonomous University of Barcelona (UAB). She obtained her PhD at the same University in 1990 for work on brain histamine receptors carried out under the supervision of Agustina García. Next, she moved to a biotech company in California (Cell Genesys, Inc.) to work on gene editing in mammalian somatic cells and leucocyte homing and inflammation. In 1994, she obtained a “reintegration” contract to join Agustina Garcia’s lab at the Institut de Biotecnologia i Biomedicina (UAB) where she studied the role of nitric oxide in glial cells. In 1996, she moved to the Department of Molecular Genetics (IRO, Barcelona) to work with Xavier Estivill in neurosensorial deafness and Down syndrome. In 2002 she joined the Center for Genomic Regulation (CRG) as a group leader. She obtained a CSIC tenure track position in 2010 and in January 2011 her lab moved to the IBMB.

Past students

Sonia Najas

Postdoctoral Researcher

Selected publications

Arranz J, Balducci E, Arató K, Sánchez-Elexpuru G, Najas S, Parras A, RebolloE, Pijuan I, Erb I, Verde G, Sahun I, Barallobre MJ, Lucas JJ, Sánchez MP, de la Luna S, Arbonés ML. Impaired development of neocortical circuits contributes to the neurological alterations in DYRK1A haploinsufficiency syndrome. Neurobiol Dis. 2019 Jul;127:210-222.

 

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 Jan 17;2(2):120-34.

 

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 Jun 12;5(6):e1289.

 

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 Jul 15;22(14):2775-84.

 

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 Apr;46(1):190-203.

 

Aug;47(2):294. PMID: 22293606. 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 Dec;12(12):1220-7.

 

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. 2010 Sep 3;7(3):367-79.

 

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 Nov;36(2):312-9.

 

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 Dec;15(6):841-53.

Fotaki V, Dierssen M, Alcántara S, Martínez S, Martí E, Casas C, Visa J, Soriano E, Estivill X, Arbonés ML. Dyrk1A haploinsufficiency affects viability and causes developmental delay and abnormal brain morphology in mice. Mol Cell Biol. 2002 Sep;22(18):6636-47

All publications

LAST 10-YEARS PUBLICATION LIST

Najas S, Pijuan I, Esteve-Codina A, Usieto S, Martinez JD, Zwijsen A, Arbonés ML, Martí E, Le Dréau G. A SMAD1/5-YAP signalling module drives radial glia self-amplification and growth of the developing cerebral cortex. Development. 2020 Jul 13;147(13):dev187005.

Rebollo E, Boix-Fabrés J, Arbones ML.  Automated macro approach to quantify synapse density in 2D confocal images from fixed immunolabeled neural tissue Sections. Methods Mol Biol. 2019;2040:71-97.

Luna J, Boni J, Cuatrecasas M, Bofill-De Ros X, Núñez-Manchón E, Gironella M, Vaquero EC, Arbones ML, de la Luna S, Fillat C. DYRK1A modulates c-MET in pancreatic ductal adenocarcinoma to drive tumour growth.  Gut. 2019 Aug;68(8):1465-1476.


Arranz J, Balducci E, Arató K, Sánchez-Elexpuru G, Najas S, Parras A, Rebollo E, Pijuan I, Erb I, Verde G, Sahun I, Barallobre MJ, Lucas JJ, Sánchez MP, de la Luna S, Arbonés MLImpaired development of neocortical circuits contributes to the neurological alterations in DYRK1A haploinsufficiency syndrome. Neurobiol Dis. 2019 Jul;127:210-222.


Arbones ML, Thomazeau A, Nakano-Kobayashi A, Hagiwara M, Delabar JM. DYRK1A and cognition: A lifelong relationship. Pharmacol Ther. 2019 Feb;194:199-221.


Luna J, Boni J, Cuatrecasas M, Bofill-De Ros X, Núñez-Manchón E, Gironella M, Vaquero EC, Arbones ML, de la Luna S, Fillat C. DYRK1A modulates c-MET in pancreatic ductal adenocarcinoma to drive tumour growth. Gut. 2019 Aug;68(8):1465-1476.


Latour A, Gu Y, Kassis N, Daubigney F, Colin C, Gausserès B, Middendorp S, Paul JL, Hindié V, Rain JC, Delabar JM, Yu E, Arbones M, Mallat M, Janel N. LPS-induced inflammation abolishes the effect of DYRK1A on IkB stability in the brain of mice. Mol Neurobiol. 2019 Feb; 56(2):963-975.


Rozen EJ, Roewenstrunk J, Barallobre MJ, Di Vona C, Jung C, Figueiredo AF, Luna J, Fillat C, Arbonés ML, Graupera M, Valverde MA, de la Luna S. DYRK1A kinase positively regulates angiogenic responses in endothelial cells. Cell Rep. 2018 May 8;23(6):1867-1878.


Najas S, Arranz J, Lochhead PA, Ashford AL, Oxley D, Delabar JM, Cook SJ, Barallobre MJ, Arbonés MLDYRK1A-mediated Cyclin D1 Degradation in Neural Stem Cells Contributes to the Neurogenic Cortical Defects in Down Syndrome. EBioMedicine. 2015 Jan 17;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 May; 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 Sep 4;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 Aug12;4:e425.


Barallobre MJ, Perier C, Bové J, Laguna A, Delabar JM, Vila M, Arbonés MLDYRK1A promotes dopaminergic neuron survival in the developing brain and in a mouse model of Parkinson’s disease. Cell Death Dis. 2014 Jun 12;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 Sep;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 May;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 Jul;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 MLTriplication of DYRK1A causes retinal structural and functional alterations in Down syndrome. Hum Mol Genet. 2013 Jul 15;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 Jul 1;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 Mar 7;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 Apr;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 Jun; 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 Sep 26;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 Dec;12(12):1220-7.


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. 2010 Sep 3;7(3):367-79.

Project funding

Analizando la función de la quinasa DYRK1A en neurogénesis y diferenciación neuronal utilizando mutantes condicionales de ratón.
MICINN: PID2019-105902RB-I00
2020 – 2023
PI: Mariona Arbonés

ReDevNeural 3.0: Un enfoque integrador para entender la lógica del desarrollo neural

MICINN: RED2018-102553-T

2020-2022

IP: Paola Bovolenta (Responsable Grupo: Mariona Arbonés)

Funciones de la quinasa DYRK1A y de los microRNAs en la neurogénesis de la corteza cerebral en desarrollo

MINECO: SAF2016-77971-R

2017-2020

IP: Mariona Arbonés

Identifying new mechanisms by which dyrk1a regulates the expansion of the cerebral cortex

Foundation Jérôme Lejeune

2017-2019

IP: María José Barallobre

DYRK protein kinases and disease


AGAUR: 2017 SGR 1163

2017-2019

IP: Susana de la Luna (Responsable Grupo: Mariona Arbonés)

REDEVNEURAL: Un enfoque integrador para entender la lógica del desarrollo neural

MINECO: BFU2016-81887-REDT


2017-2019

IP: Paola Bovolenta (Responsable Grupo: Mariona Arbonés)

Mecanismos patogénicos del síndrome de discapacidad intelectual causado por mutaciones en el gen DYRK1A

Fundación Alicia Koplowitz (FAK-2016)

2016-2019

IP: Mariona Arbonés

Generando diversidad neuronal

MINECO: BFU2014-55738-REDT

2014-2016

IP: Paola Bovolenta (Responsable Grupo: Mariona Arbonés)

Estudio de los mecanismos moleculares que regulan el desarrollo de la corteza cerebral y su implicación en trastornos del neurodesarrollo

MINECO: SAF2013-46676-P

2014-2016

IP: Mariona Arbonés

Estudio de las bases celulares y moleculares de procesos del neurodesarrollo regulados por proteínas quinasa y su implicación en aneuploidías del cromosoma 21

AGAUR: 2014 SGR 674

2014-2016

IP: Susana de la Luna (Responsable Grupo: Mariona Arbonés)

Deciphering how triplication of DYRK1A impacts in early brain neurogenesis

Foundation Jérôme Lejeune

2013 –2015

IP: Mariona Arbonés

Análisis de las funciones de la proteína quinasa del síndrome de Down DYRK1A en el desarrollo de la corteza cerebral y de las neuronas dopaminérgicas mesencefálicas

CSIC

2011–2012

IP: Mariona Arbonés

Analizando las funciones de la proteína quinasa DYRK1A del síndrome de Down en la corteza cerebral y las neuronas dopaminérgicas del ratón

MICINN: SAF2010-17004

2010–2014

IP: Mariona Arbonés

Estudio de las bases celulares y moleculares de procesos del neurodesarrollo regulados por proteínas quinasa y su implicación en aneuploidías del cromosoma 21

AGAUR: 2009 SGR 1464

2009-2013

IP: Susana de la Luna (Responsable Grupo: Mariona Arbonés)

Vacancies/Jobs

If you are interested in joining the lab as postdoc or PhD student please send us your CV and cover letter: Mariona Arbonés (marbmc@ibmb.csic.es)

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