Developmental neurobiology and regeneration
Eduardo Soriano
Principal Investigator
Professor (Cell Biology Dept. - UB)
Office Tel : +34 93 403 71 17 +34 93 40215 39
e-mail : eduardo.soriano
irbbarcelona.org
Background
Brain development is a complex process which involves several sequential steps: regional determination, specification of neuronal cell types, control of cell migration, guidance and formation of neural connective networks, and activity-dependent synaptic plasticity.
The correct functioning of all these processes is essential for the construction of the brain. Genetic and molecular alterations of these processes are always associated with anatomical malformations and physiological dysfunctions of this organ. Recent research has demonstrated that these steps are exquisitely controlled by a variety of molecular and cellular mechanisms, including expression of specific transcription factors, activity of morphogens and growth factors, guidance molecules and extracellular proteins, and synaptic activity.
Our research focuses on the identification of new genes involved in these processes, and the characterization of the intracellular signalling pathways activated in growth cones in response to extracellular signals. Moreover, it is known that the adult brain does not regenerate, either after lesions or disease-associated cell-death processes. Studies on the mechanisms that govern the normal development and growth of the nervous system are essential to explain the lack of spontaneous brain repair in adult tissue and to design new regenerative approaches to repair brain lesions.
Research Interests
Our main goal is to identify and characterize new signalling pathways and new genes that participate in the development of the Nervous System, in particular of the cerebral cortex.
We study the role of new genes, previously identified in a substracted cDNA library (eg., the adhesion proteins tspan-5 and Podocalyxin; the beta-catenin-like protein Alex-3), in neural migration and guidance, formation of neural connections, and neural maturation.
We combine biochemical and molecular biology approaches with functional in vitro models. Furthermore, transgenic and knock-out mice are generated to ascertain the function of these genes in vivo. In addition, we dissect new signalling pathways activated by two classical guidance cues, Netrin 1 and Reelin.
We also study the participation of Pyk1, a new cytoslic tyrosine kinase cloned by the group, and also SNARE proteins regulating exocytosis at the growth cone in the signalling pathways activated by Netrin 1 and Reelin.
Finally, our research also addresses new regenerative and cell therapy-based approaches for the repair of lesioned neurons and for the replacement of degenerated, dead neurons in animal models of neurodegenerative diseases.
Research Lines
Our research focuses on the identification of genes and epigenetic factors that govern the development of the cerebral cortex. In particular, we study the molecular factors that regulate neural migration and the formation of specific neural connections.
Major efforts are devoted to determining the role of new genes in these events, by using in vitro cell technologies and murine animal models generated in the laboratory (conditional transgenics and knock-outs). We also dissect the intracellular cascades activated by guidance molecules in growth cones during neural development (receptors, kinases, synaptic proteins, adaptors and activation of transcription factors).
Our team has developed an in vitro model for nerve regeneration by using organotypic slice cultures. In this preparation, neurons can be manipulated easily and bioactive reagents can be tested for the promotion of nerve regeneration. Furthermore, regenerating axons can be visualized directly and monitored under the microscope by labelling with fluorescent markers such as GFP.
Our research involves state-of-the-art techniques in the fields of cell and molecular neurobiology, neurodevelopment and neuroregeneration. We use several experimental approaches, including neural transplantation, the genetic engineering of cell lines expressing genes with axogenic properties, and the generation of transgenic mice, to ameliorate genetic developmental disorders of the cerebral cortex and to promote axonal regeneration of damaged, neural axotomized connections.
A second approach explores the potential of neural stem cells (neurospheres) obtained from adult tissue for neuronal repair; we also aim to characterize new factors that control their proliferative potential and their differentiation into particular types of cortical neurons.
Funding
This group receives financial support from the following sources:
- Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo (FIS- Spanish National Institute of Health)
- Ministerio de Educación y Ciencia (MEC - Spanish Ministry of Science and Education)
- Generalitat de Catalunya (Government of Catalonia)
- Fundació “la Caixa” (La Caixa Foundation)
More info
Developmental neurobiology and regeneration
Amyloid precursor protein cytoplasmic domain antagonizes reelin neurite outgrowth inhibition of hippocampal neurons
Hoareau C, Borrell V, Soriano E, Krebs MO, Prochiantz A and Allinquant B
Neurobiol Aging, 29 (4), 542-553 (2008)
Enhanced susceptibility of Prnp-deficient mice to kainate-induced seizures, neuronal apoptosis, and death: Role of AMPA/kainate receptors
Rangel A, Burgaya F, Gavín R, Soriano E, Aguzzi A and del Río JA
J Neurosci Res, 85 (12), 2741-2755 (2007)
Involvement of the myelin-associated inhibitor Nogo-A in early cortical development and neuronal maturation
Mingorance-Le Meur A, Zheng B, Soriano E and del Río JA
Cereb Cortex, 17 (10), 2375-2386 (2007)
Bcl-2 overexpression delays caspase-3 activation and rescues cerebellar degeneration in prion-deficient mice that overexpress amino-terminally truncated prion
Nicolas O, Gavin R, Braun N, Urena JM, Fontana X, Soriano E, Aguzzi A and del Rio JA
FASEB J, 21 (12), 3107-3117 (2007)
Reelin and mDab1 regulate the development of hippocampal connections
Borrell V, Pujadas L, Simo S, Dura D, Sole M, Cooper JA, del Rio JA and Soriano E
Mol Cell Neurosci, 36 (2), 158-173 (2007)
Mechanism suppressing glycogen synthesis in neurons and its demise in progressive myoclonus epilepsy
Vilchez D, Ros S, Cifuentes D, Pujadas L, Vallès J, García-Fojeda B, Criado-García O, Fernández-Sánchez E, Medraño-Fernández I, Domínguez J, García-Rocha M, Soriano E, Rodríguez de Córdoba S and Guinovart JJ
Nat Neurosci, 10 (11), 1407-1413 (2007)
Reelin induces the detachment of postnatal subventricular zone cells and the expression of the Egr-1 through Erk1/2 activation
Simó S, Pujadas L, Segura MF, La Torre A, del Río JA, Ureña JM, Comella JX and Soriano E
Cereb Cortex, 17 (2), 294-303 (2007)
Cerebellar GABAergic progenitors adopt an external granule cell-like phenotype in the absence of Ptf1a transcription factor expression
Pascual M, Abasolo I, Mingorance-Le Meur A, Martinez A, Del Río JA, Wright CV, Real FX and Soriano E
Proc Natl Acad Sci USA, 104 (12), 5193-5198 (2007)
Expression patterns of MLC1 protein in the central and peripheral nervous systems
Teijido O, Casaroli-Marano R, Kharkovets T, Aguado F, Zorzano A, Palacín M, Soriano E, Martínez A and Estévez R
Neurobiol Dis, 26 (3), 532-545 (2007)
The long form of Fas apoptotic inhibitory molecule is expressed specifically in neurons and protects them against death receptor-triggered apoptosis
Segura MF, Sole C, Pascual M, Moubarak RS, Perez-Garcia MJ, Gozzelino R, Iglesias V, Badiola N, Bayascas JR, Llecha N, Rodriguez-Alvarez J, Soriano E, Yuste VJ and Comella JX
J Neurosci, 27 (42), 11228-11241 (2007)
Overcoming chondroitin sulphate proteoglycan inhibition of axon growth in the injured brain: lessons from chondroitinase ABC
Del Rio JA and Soriano E
Curr Pharm Des, 13 (24), 2485-2492 (2007)
Expression pattern of ACK1 tyrosine kinase during brain development in the mouse
La Torre A, del Rio JA, Soriano E and Ureña JM
Gene Expr Patterns, 6 (8), 886-892 (2006)
Semaphorin 6C leads to GSK-3-dependent growth cone collapse and redistributes after entorhino-hippocampal axotomy
Burgaya F, Fontana X, Martínez A, Montolio M, Mingorance A, Simó S, del Río JA and Soriano E
Mol Cell Neurosci, 33 (3), 321-334 (2006)
Nogo-A expression in the human hippocampus in normal aging and in Alzheimer disease
Gil V, Nicolas O, Mingorance A, Ureña JM, Tang BL, Hirata T, Sáez-Valero J, Ferrer I, Soriano E and del Río JA
J Neuropathol Exp Neurol, 65 (5), 433-444 (2006)
Regeneration of lesioned entorhino-hippocampal axons in vitro by combined degradation of inhibitory proteoglycans and blockade of Nogo-66/NgR signaling
Mingorance A, Solé M, Munetón V, Martínez A, Nieto-Sampedro M, Soriano E and del Río JA
FASEB J, 20 (3), 491-493 (2006)
Expression of discoidin domain receptor 1 during mouse brain development follows the progress of myelination
Franco-Pons N, Virgos C, Vogel WF, Ureña JM, Soriano E, del Rio JA and Vilella E
Neuroscience, 140 (2), 463-475 (2006)
Activation of the nonreceptor protein tyrosine kinase Ack by multiple extracellular stimuli
Galisteo ML, Yang Y, Ureña J and Schlessinger J
Proc Natl Acad Sci USA, 103 (26), 9796-9801 (2006)
Age-dependent spontaneous hyperexcitability and impairment of GABAergic function in the hippocampus of mice lacking trkB
Carmona MA, Pozas E, Martínez A, Espinosa-Parrilla JF, Soriano E and Aguado F
Cereb Cortex, 16 (1), 47-63 (2006)
Control of neuronal branching by the death receptor CD95 (Fas/Apo-1)
Zuliani C, Kleber S, Klussmann S, Wenger T, Kenzelmann M, Schreglmann N, Martinez A, del Rio JA, Soriano E, Vodrazka P, Kuner R, Groene HJ, Herr I, Krammer PH and Martin-Villalba A
Cell Death Differ, 13 (1), 31-40 (2006)
Netrin1 exerts a chemorepulsive effect on migrating cerebellar interneurons in a Dcc-independent way
Guijarro P, Simó S, Pascual M, Abasolo I, del Río JA and Soriano E
Mol Cell Neurosci, 33 (4), 389-400 (2006)
Ephrin-A5 modulates the topographic mapping and connectivity of commissural axons in murine hippocampus
Otal R, Burgaya F, Frisén J, Soriano E and Martínez A
Neuroscience, 141 (1), 109-121 (2006)
BDNF-modulated spatial organization of Cajal-Retzius and GABAergic neurons in the marginal zone plays a role in the development of cortical organization
Alcantara S, Pozas E, Ibañez Cl and Soriano E
Cereb Cortex, 16 (4), 487-499 (2006)
Reelin expression and glycosylation patterns are altered in Alzheimer's disease
Botella-López A, Burgaya F, Gavín R, García-Ayllón MS, Gómez-Tortosa E, Peña-Casanova J, Ureña JM, Del Río JA, Blesa R, Soriano E and Sáez-Valero J
Proc Natl Acad Sci USA, 103 (14), 5573-5578 (2006)
The cells of cajal-retzius: still a mystery one century after
Soriano E and del Río JA
Neuron, 46 (3), 389-394 (2005)
Overexpression of myelin-associated glycoprotein after axotomy of the perforant pathway
Mingorance A, Fontana X, Soriano E and del Río JA
Mol Cell Neurosci, 29 (3), 471-483 (2005)
The Netrin family of guidance factors: emphasis on Netrin-1 signalling
Barallobre MJ, Pascual M, del Río JA and Soriano E
Brain Res Brain Res Rev, 49 (1), 22-47 (2005)
A role of MAP1B in Reelin-dependent neuronal migration
González-Billault C, del Río JA, Ureña JM, Jiménez-Mateos EM, Barallobre MJ, Pascual M, Pujadas L, Simó S, Torre AL, Gavin R, Wandosell F, Soriano E and Avila J
Cereb Cortex, 15 (8), 1134-1145 (2005)
Mouse neuron navigator 1, a novel microtubule-associated protein involved in neuronal migration
Martínez-López MJ, Alcántara S, Mascaró C, Pérez-Brangulí F, Ruiz-Lozano P, Maes T, Soriano E and Buesa C
Mol Cell Neurosci, 28 (4), 599-612 (2005)
Bcl-2 overexpression does not promote axonal regeneration of the entorhino-hippocampal connections in vitro after axotomy
Solé M, Fontana X, Gavín R, Soriano E and del Río JA
Brain Res, 1020 (1-2), 204-209 (2004)
MAP1B is required for Netrin 1 signaling in neuronal migration and axonal guidance
Del Río JA, González-Billault C, Ureña JM, Jiménez EM, Barallobre MJ, Pascual M, Pujadas L, Simó S, La Torre A, Wandosell F, Avila J and Soriano E
Curr Biol, 14 (10), 840-850 (2004)
Coordinated functions of Netrin-1 and Class 3 secreted Semaphorins in the guidance of reciprocal septohippocampal connections
Pascual M, Pozas E, Barallobre MJ, Tessier-Lavigne M and Soriano E
Mol Cell Neurosci, 26 (1), 24-33 (2004)
BDNF regulates spontaneous correlated activity at early developmental stages by increasing synaptogenesis and expression of the K+/Cl- co-transporter KCC2
Aguado F, Carmona MA, Pozas E, Aguiló A, Martínez-Guijarro FJ, Alcantara S, Borrell V, Yuste R, Ibañez CF and Soriano E
Development, 130 (7), 1267-1280 (2003)
Developmental neurobiology and regeneration
Eduardo Soriano
Principal Investigator
Professor (Cell Biology Dept. - UB)
Office Tel : +34 93 403 71 17 +34 93 40215 39
e-mail : eduardo.soriano
irbbarcelona.org
Research Associate
José Antonio Del Río Fernández
tel +34 93 403 71 18
joseantonio.delrio
irbbarcelona.org
Jesús Ureña Bares
tel +34 93 403 71 19
jesus.urena
irbbarcelona.org
Ferrán Burgaya Márquez
tel +34 93 403 71 19
ferran.burgaya
irbbarcelona.org
Albert Martínez García
tel +34 93 403 71 19
albert.martinez
irbbarcelona.org
Postdoctoral Fellow
Marta Pascual Sánche
tel +34 93 403 71 19
marta.pascual
irbbarcelona.org
Ashraf J. M. Muhaisen
tel +34 93 403 71 19
ashraf.muhaisen
irbbarcelona.org
Tiziana Cotrufo
tel +34 93 403 71 19
tiziana.cotrufo
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Rosalina Gavín Marín
tel +34 93 403 71 19
rosalina.marin
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Lluís Pujadas Puigdomènech
tel +34 93 403 71 19
lluis.pujadas
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Delphine Meffre
tel +34 93 403 71 19
delphine.meffre
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Katharina Kreymborg
tel +34 93 403 7119
katharina.kreymborg
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PhD Student
Guillermo López Domènech
tel +34 93 403 71 19
guillermo.lopez
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Alejandra H. Rangel Rincones
tel +34 93 403 71 19
alejandra.rangel
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Vanessa Gil Fernández
tel +34 93 403 71 19
vanessa.gil
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Josep Oriol Nicolàs Pallejà
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josep.nicolas
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Oriol Ros i Torres
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Oscar Seira Oriach
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Sara Esmeralda Rubio Abejón
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Giulia Fuschini
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giulia.fuschini
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Carles Bosch Piñol
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Roman Serrat Reñe
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roman.serrat
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Esther Pérez Martínez
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esther.perez
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Beatriz García
tel +34 93 403 71 19
beatriz.garcia
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Research Assistant
Mª del Carmen López Rodríguez
tel +34 93 403 71 19
maria.romero
irbbarcelona.org
Hagar Lock
tel +34 93 403 71 19
hagar.lock
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Lab Manager
Estefanía Márquez
tel +34 93 403 47 55
estefania.marquez
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Lab Technician
Lucas Brunso Welker
lucas.brunso
irbbarcelona.org