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
2007
Expression patterns of MLC1 protein in the central and peripheral nervous systems
Teijido O, Casaroli-Marano R, Kharkovets T, Aguado F, Zorzano A, Palacin M, Soriano E, Martinez A, Estevez R.
Neurobiol Dis. 26, pag. 532-545 PMID: 17434314 [PubMed - indexed for MEDLINE], Vol: 3, 26 Jun (2007)
Mechanism suppressing glycogen synthesis in neurons and its demise in progressive myoclonus epilepsy
Vilchez D., Ros S., Cifuentes D., Pujadas L.l., Vallès J., García-Fojeda B., Criado-García O., Fernández-Sánchez E., Medraño M.I., Domínguez J., García Rocha M., Soriano E., Rodríguez de Córdoba S. & Guinovart J.J.
Nature Neuroscience 10, pag. 1407-1413 (2007)
Cerebellar GABAergic progenitors adopt an external granule cell-like phenotype in the absecne 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, pag. 5193-5198 (2007)
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, pag. 2741-2755, Vol: 12 (2007)
Reelin induces the detachment of postnatal subventricular zone cells and expression of the Erg-1 through Erk 1/2 activation
Simó S., Pujadas L., Segura M.F., La Torre A., Del Río J.A., Ureña J., Comella J., and Soriano E
Cereb Cortex 17, pag. 294-303, Vol: 2 (2007)
APP 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, Vol: In press (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, pag. 2375-2386, Vol: 10 (2007)
The long form of Fas apoptotic inhibitory molecule is expressed specifically in neurons and protects them against death receptor-triggered apoptosis
2. 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, Comella JX.
J. Neuroscience 27, pag. 11228-11241 (2007)
GABAergic cerebellar progenitors adopt an external granule cell-like phenotype in the absence of Ptf1a transcription factor expression
Pascual M., Abasolo I., Le Meur-Mingorance A., Martínez A., Del Río J.A., Wright C., Real F.X. and Soriano E.
PNAS 104, pag. 5193-5198, Vol: 12 (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, del Rio JA.
FASEB J. 21, pag. 3107-3117, Vol: 12 (2007)
Overcoming chondroitin sulphate proteoglycan inhibition of axon growth in the injured brain: lessons from chondroitinase ABC
Del Rio JA, Soriano E.
Curr Pharm Des. 13, pag. 2485-2492, Vol: 24 (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, Soriano E.
Mol Cell Neurosci. 36, pag. 158-173 (2007)
2006
Regeneration of lesioned entorhino-hippocampal axons in vitro bycombined degradation of inhibitory proteoglycans and blockade ofNogo-66/NgR signaling
Mingorance A., Sole M., Muneton V., Martinez A., Nieto-Sampedro M., Soriano E., Del Rio J.A.
FASEB J., Vol: [Epub ahead of print], 11 Jan (2006)
BDNF-modulated spatial organisation of Cajal-Retzius and GABAergic neurons in the marginal zone plays a role in the developmento of cortical organisation
Alcantara S., Pozas E., Ibañez Cl. and Soriano E.
Cereb Cortex 16, pag. 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 MS., Peña-Casanova J., Ureña J., del Río JA., Blesa R., Soriano E. and Sáez-Valero J.
Proc Natl Acad Sci USA 103, pag. 5507-5578 (2006)
Semaphorin 6C leads to GSK-3-dependent growth cone collapse and redistributes after entorhino-hippocampal axotomy
Burgaya F., Fontana X., Martinez A., Montolio M., Mingorance A., Simo S., Del Rio JA., and Soriano E.
Mol Cell Neurosci 33, pag. 321-334 (2006)
Age-dependent spontaneous hyperexcitability and impairment of GABAergic function in the hippocampus of mice lacking trkB
Carmona MA., Pozas E., Martinez A., Espinosa-Parrilla J., Soriano E. and Aguado J.
Cereb Cortex 16, pag. 47-63 (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 Río JA. and Vilella E.
Neuroscience 140, pag. 463-475 (2006)
Activation of the nonreceptor protein tyrosine kinase Ack by multiple extracellular stimuli
Galisteo ML., Yang Y. Urena J. and Schlessinger J.
Proc Natl Acad Sci USA 103, pag. 9796-9801 (2006)
Nogo-A expression in the human hippocampus in normal aging and in Alzheimer disease
Gil V., Nicolás O., Mingorance A., Ureña JM., Tang BL., Hirata T., Saez-Valero J., Ferrer I., Soriano E. and Del Río JA.
J Neuropathol Exp Neurol 65, pag. 433-444 (2006)
Netrin1 exerts a chemorepulsive effect on migrating cerebellar interneurons in a Dcc-independent way
Guijarro P., Simo S., Pascual M., Abasolo I., Del Río JA., and Soriano E.
Mol Cell Neurosci 33, pag. 389-400 (2006)
Expression pattern of ACK1 tyrosine kinase during brain development in the mouse
La Torre A., Del Río JA., Soriano E., and Ureña JM.
Gene Expr Patterns 6, pag. 886-892 (2006)
Ephrin a-5 modulates the topographic mapping and connectivity of commissural axons in murine hippocampus
Otal R., Burgaya F., Frisen J., Soriano E., and Martinez A.
Neuroscience 141, pag. 109-121 (2006)
Control of neuronal branching by the death receptor CD95 (Fas/Apo-1)
Zuliani C., Kleber S., Klussmann S., Wenger T., Kenxelmann M., Schreglmann N., Martínez A., Del Río JA., Soriano E., Vodrazka P., Kuner R., Groene HJ., Herr I., Krammer PH and Martin-Villalba A.
Cell Death Differ 13, pag. 31-40 (2006)
2005
Overexpression of myelin-associated glycoprotein after axotomy of the perforant pathway
Mingorance A., Fontana X., Soriano E., Del Rio J.A.
Mol Cell Neuroscience 29, pag. 471-483 (2005)
The cells of cajal-retzius: still a mystery one century after
Soriano E., and J.A. Del Río
Neuron, 46:389-94 (2005) 46, pag. 389-394 (2005)
The Netrin family of guidance factors: emphasis on Netrin-1 signalling
Barallobre, M.J., Pascual M., Del Río, J.A. and Soriano E.
Brain Reseach Reviews, 49, pag. 22-47 (2005)
Mouse Neuron Navigator-1, a novel microtubule-associated involved in neuronal migration
Martínez-López M. J., Alcantara S., Mascaró C., Pérez-Francolí F., Ruiz-Lozano P., Maes T., Soriano E. and Buesa C.
Molecular and Cellular Neuroscience 28, pag. 599-612 (2005)
A role of MAP1B in Reelin-dependent Neuronal Migration
González-Guillault C., Del Río J.A., Ureña J.M., Jiménez E.M., Barallobre M.J., Pascual M., Simó S., Pujades LL., Latorre A.,Wandosell F., Soriano E. and Avila J.
Cerebral Cortex 15, pag. 1134-1145, Vol: 8 (2005)
2004
Bcl-2 overexpression does not promote axonal regeneration of the entorhinohippocampal connections in vitro after axotomy
Sole M., Fontana X., Gavin R., Soriano E., Del Río JA.
Brain Research 10, pag. 204-209 (2004)
MAP1B is required for netrin 1 signaling in neuronal migration and axonal guidance
DelRío J.A., González-Guillault C., Ureña J.M., Jiménez E.M., Barallobre M.J., Pascual M., Pujadas LL., Simó S., Latorre A., Wandosell F, Avila J., and Soriano E.
Current Biology 25, pag. 840-850 (2004)
Coordinated functions of Netrin 1 and class III secreted Sempahorins in the guidance of reciprocal septohippocampal connections
Pascual M., Pozas E., Tessier-Lavigne, M., and Soriano E
Molecular and Cellular Neuroscience 26, pag. 24-33 (2004)
2003
BDNF regulates spontaneous correlated activity at early development stages by increasing synaptogenesis and expression of the K+/CL- co-transporter KCC2
Aguado F., Carmona M.A., Pozas E., Aguilo A., Martínez-Guijarro F.J., Alcántara S., Borrell V., Yuste R., Ibáñez C.F. and Soriano E.
Development 130, pag. 1267-1280, Vol: 7 (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
Rosa Andrés Ventura
tel +34 93 403 71 19
rosa.andres
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
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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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PhD Student
Anna La Torre i Vila
tel +34 93 403 71 19
anna.latorre
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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
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Josep Oriol Nicolàs Pallejà
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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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Carles Bosch Piñol
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roman.serrat
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Esther Pérez Martínez
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esther.perez
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Research Assistant
Mª del Carmen López Rodríguez
tel +34 93 403 71 19
maria.romero
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Eva María Pastor
tel +34 93 403 71 31
eva.pastor
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Hagar Lock
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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
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