Neurogénesis y expansión cortical

Líneas de investigación

Nuestro laboratorio está interesado en comprender los mecanismos celulares y moleculares que controlan la expansión de la corteza cerebral a lo largo de la escala evolutiva de los mamíferos. La corteza cerebral es la mayor estructura en el cerebro y es responsable, entre otras, de las funciones cognitivas superiores que distinguen a los humanos de los otros mamíferos. Se cree que el extraordinario crecimiento en tamaño de la corteza cerebral que se observa en la escala evolutiva de los mamíferos es responsable del aumento concomitante en capacidad intelectual. Esta expansión evolutiva de la corteza cerebral está recapitulada durante el desarrollo en mamíferos superiores, cuando la corteza cerebral embrionaria sufre un crecimiento masivo en área superficial, y se pliega sobre si misma en patrones altamente estereotípicos.

En los últimos años se han identificado múltiples mutaciones genéticas causantes de retraso mental o reducción de la capacidad intelectual en humanos. Estas mutaciones se han relacionado sistemáticamente con defectos en el desarrollo cortical durante la embriogénesis, y estudios funcionales en roedores han mostrado que muchos de estos genes desempeñan funciones esenciales en distintos aspectos de la migración neuronal cortical o en el plegamiento del manto cortical.

Nosotros estamos intensados en identificar y analizar los mecanismos básicos implicados en la expansión normal y el plegamiento de la corteza cerebral en mamíferos superiores. Con este fin utilizamos una combinación de herramientas genéticas (electroporación in vivo e in vitro, vectores virales, ratones transgénicos y knock-out), embriología experimental, técnicas de imagen de ultima generación y métodos histológicos y de biología celular y molecular estándar, usando varias especies como modelo experimental. En la actualidad nuestros esfuerzos se centran en comprender la función de las células de Cajal-Retzius y los progenitores intermedios en la expansión tangencial versus radial de la corteza cerebral, y en la formación de giros en posiciones estereotipadas en la corteza cerebral durante su desarrollo.

Web CortEvo-scFerret developing cerebral cortex
Del-Valle-Antón et al., Science Advances 2024

Publicaciones relevantes

Multiple parallel cell lineages in the developing mammalian cerebral cortex. Del-Valle-Anton L, Amin S, Cimino D, Neuhaus F, Dvoretskova E, Fernández V, Babal YK, Garcia-Frigola C, Prieto-Colomina A, Murcia-Ramón R, Nomura Y, Cárdenas A, Feng C, Moreno-Bravo, J.A, Götz, M, Mayer C and Borrell V. Science Advances. 2024 10 (13), eadn9998 https://doi.org/10.1126/sciadv.adn9998
Gene regulatory landscape of cerebral cortex folding Singh A, Del-Valle-Anton L, de Juan Romero C, Zhang Z, Fernández Ortuño E, Mahesh A, Espinós A, Soler R, Cárdenas A, Fernández V, Lusby R, Tiwari V K and Borrell V. Science Advances. 2024 10(23), eadn1640 https://doi.org/10.1126/sciadv.adn1640
Developmental mechanisms of gyrification. Fernández V, Borrell V. Curr Opin Neurobiol. 2023 80: 102711 https://10.1016/j.conb.2023.102711
Structural basis of envelope and phase intrinsic coupling modes in the cerebral cortex. Messé A, Hollensteiner KJ, Delettre C, Dell L-A, Pieper F, Nentwig LJ, Galindo-Leon EE, Larrat B, Mériaux S, Mangin JF, Reillo I, de Juan Romero C, Borrell V, Engler G, Toro R, Engel AK, Hilgetag CC Neuroimage. 2023 276: 120212 https://doi.org/10.1016/j.neuroimage.2023.120212
Theta/gamma Co-modulation Disruption After NMDAr Blockade by MK-801 Is Associated with Spatial Working Memory Deficits in Mice. Abad-Perez P, Molina-Payá F.J., Martínez-Otero L, Borrell V, Redondo RL, Brotons-Mas JR . Neuroscience. 2023 519: 162-176 https://doi.org/10.1016/j.neuroscience.2023.03.022
Secondary loss of miR-3607 reduced cortical progenitor amplification during rodent evolution Chinnappa K, Cárdenas A, Prieto-Colomina A, Villalba A, Márquez-Galera Á, Soler R, Nomura Y, Llorens E, Tomasello U, López-Atalaya JP, Borrell V Sci Adv 2022 8(2):eabj4010 https://doi.org/10.1126/sciadv.abj4010
Specific contribution of Reelin expressed by Cajal–Retzius cells or GABAergic interneurons to cortical lamination Alba Vílchez-Acosta, Yasmina Manso, Adrián Cárdenas, Alba Elias-Tersa, Magdalena Martínez-Losa, Marta Pascual, Manuel Álvarez-Dolado, Angus C. Nairn, Víctor Borrell, Eduardo Soriano PNAS 2022 119 (37): e2120079119 https://doi.org/10.1073/pnas.2120079119
Repression of Irs2 by let-7 miRNAs is essential for homeostasis of the telencephalic neuroepithelium Fernández V, Martínez-Martínez MÁ, Prieto-Colomina A, Cárdenas A, Soler R, Dori M, Tomasello U, Nomura Y, López-Atalaya JP, Calegari F, Borrell V EMBO J 2020 39(21):e105479 https://doi.org/10.15252/embj.2020105479
A Retino-retinal Projection Guided by Unc5c Emerged in Species with Retinal Waves Murcia-Belmonte V, Coca Y, Vegar C, Negueruela S, de Juan Romero C, Valiño AJ, Sala S, DaSilva R, Kania A, Borrell V, Martinez LM, Erskine L, Herrera E Current Biology 2019 29(7):1149 https://doi.org/10.1016/j.cub.2019.02.052
Evolution of Cortical Neurogenesis in Amniotes Controlled by Robo Signaling Levels Cardenas A, Villalba A, de Juan Romero C, Pico E, Kyrousi C, Tzika AC, Tessier-Lavigne M, Ma L, Drukker M, Cappello S, Borrell V Cell 2018 174(3):590 https://doi.org/10.1016/j.cell.2018.06.007

Jefe de grupo

Víctor Borrell Franco Profesor de Investigación CSIC

Investigador asociado

Jorge Brotons Mas Univ. Cardenal Herrera

Investigador postdoctoral

Adrián Cárdenas Castelló

Investigador postdoctoral

Virginia Fernández Martínez

Investigador postdoctoral

Lara López Gónzalez

Investigador predoctoral

Pablo Abad Pérez

Investigador predoctoral

Investigador predoctoral

Alexandre Espinos Soro

Investigador predoctoral

Eduardo Fernández Ortuño

Investigador predoctoral

Investigador predoctoral

Laura Pérez Grau

Investigador predoctoral

Soledad Pérez Sánchez

Investigador predoctoral

Anna Prieto Colomina

Investigador predoctoral

Rafael Soler Ortuño

Personal técnico

Pablo Aracil Climent

Personal técnico

Esther Llorens Alvarez

Personal administración

Vasiliki Katsomaliari Asistente laboratorio

Multiple parallel cell lineages in the developing mammalian cerebral cortex. Del-Valle-Anton L, Amin S, Cimino D, Neuhaus F, Dvoretskova E, Fernández V, Babal YK, Garcia-Frigola C, Prieto-Colomina A, Murcia-Ramón R, Nomura Y, Cárdenas A, Feng C, Moreno-Bravo, J.A, Götz, M, Mayer C and Borrell V. Science Advances. 2024 10 (13), eadn9998 https://doi.org/10.1126/sciadv.adn9998
Gene regulatory landscape of cerebral cortex folding Singh A, Del-Valle-Anton L, de Juan Romero C, Zhang Z, Fernández Ortuño E, Mahesh A, Espinós A, Soler R, Cárdenas A, Fernández V, Lusby R, Tiwari V K and Borrell V. Science Advances. 2024 10(23), eadn1640 https://doi.org/10.1126/sciadv.adn1640
Developmental mechanisms of gyrification. Fernández V, Borrell V. Curr Opin Neurobiol. 2023 80: 102711 https://10.1016/j.conb.2023.102711
Structural basis of envelope and phase intrinsic coupling modes in the cerebral cortex. Messé A, Hollensteiner KJ, Delettre C, Dell L-A, Pieper F, Nentwig LJ, Galindo-Leon EE, Larrat B, Mériaux S, Mangin JF, Reillo I, de Juan Romero C, Borrell V, Engler G, Toro R, Engel AK, Hilgetag CC Neuroimage. 2023 276: 120212 https://doi.org/10.1016/j.neuroimage.2023.120212
Theta/gamma Co-modulation Disruption After NMDAr Blockade by MK-801 Is Associated with Spatial Working Memory Deficits in Mice. Abad-Perez P, Molina-Payá F.J., Martínez-Otero L, Borrell V, Redondo RL, Brotons-Mas JR . Neuroscience. 2023 519: 162-176 https://doi.org/10.1016/j.neuroscience.2023.03.022
Neocortical Neurogenesis in Amniote Evolution. Virginia Fernández, Víctor Borrell Neocortical Neurogenesis in Development and Evolution. 2023 Chapter 5: 83-105; Book Editor(s):Wieland Huttner https://doi.org/10.1002/9781119860914.ch5
Folding brains: from development to disease modeling. Del Valle Anton L, Borrell V. Physiol Rev. 2022 102(2): 511-550 - Review https://doi.org/10.1152/physrev.00016.2021
miR-137 and miR-122, two outer subventricular zone non-coding RNAs, regulate basal progenitor expansion and neuronal differentiation. Tomasello U, Klingler E, Niquille M, Mule N, Santinha AJ, de Vevey L, Prados J, Platt RJ, Borrell V, Jabaudon D, Dayer A Cell Rep. 2022 38(7): art 110381 https://doi.org/10.1016/j.celrep.2022.110381
Secondary loss of miR-3607 reduced cortical progenitor amplification during rodent evolution Chinnappa K, Cárdenas A, Prieto-Colomina A, Villalba A, Márquez-Galera Á, Soler R, Nomura Y, Llorens E, Tomasello U, López-Atalaya JP, Borrell V Sci Adv 2022 8(2):eabj4010 https://doi.org/10.1126/sciadv.abj4010
Specific contribution of Reelin expressed by Cajal–Retzius cells or GABAergic interneurons to cortical lamination Alba Vílchez-Acosta, Yasmina Manso, Adrián Cárdenas, Alba Elias-Tersa, Magdalena Martínez-Losa, Marta Pascual, Manuel Álvarez-Dolado, Angus C. Nairn, Víctor Borrell, Eduardo Soriano PNAS 2022 119 (37): e2120079119 https://doi.org/10.1073/pnas.2120079119
Evolution of genetic mechanisms regulating cortical neurogenesis. Espinós, A., Fernández-Ortuño, E., Negri, E., Borrell, V. Dev Neurobiol . 2022 82 (5): 428-453 Review https://doi.org/10.1002/dneu.22891
A protocol for in ovo electroporation of chicken and snake embryos to study forebrain development Cardenas A, Borrell V STAR Protoc 2021 2(3):100692 https://doi.org/10.1016/j.xpro.2021.100692
Editorial: The Extracellular Environment in Controlling Neuronal Migration During Neocortical Development Hirota Y, Ohtaka-Maruyama C, Borrell V Front Cell Dev Biol 2021 9:673825 https://doi.org/10.3389/fcell.2021.673825
MiRNAs in early brain development and pediatric cancer: At the intersection between healthy and diseased embryonic development Prieto-Colomina A, Fernández V, Chinnappa K, Borrell V BioEssays 2021 43(7):e2100073 https://doi.org/10.1002/bies.202100073
Protomapped by the pros: Proneural factors pattern cortex folding Borrell, Victor Neuron 2021 109(18):2797 https://doi.org/10.1016/j.neuron.2021.08.007
The regulation of cortical neurogenesis Villalba A, Gotz M Borrel, V Curr Top Dev Biol 2021 5,917361111 https://doi.org/10.1016/bs.ctdb.2020.10.003
The regulation of cortical neurogenesis Villalba A, Goetz M, Borrell V Curr Top Dev Biol 2021 5,917361111 https://doi.org/10.1016/bs.ctdb.2020.10.003
Molecular and cellular evolution of corticogenesis in amniotes Cárdenas A, Borrell V Cell Mol Life Sci 2020 77(8):1435 https://doi.org/10.1007/s00018-019-03315-x
Repression of Irs2 by let-7 miRNAs is essential for homeostasis of the telencephalic neuroepithelium Fernández V, Martínez-Martínez MÁ, Prieto-Colomina A, Cárdenas A, Soler R, Dori M, Tomasello U, Nomura Y, López-Atalaya JP, Calegari F, Borrell V EMBO J 2020 39(21):e105479 https://doi.org/10.15252/embj.2020105479
The Extracellular Matrix in the Evolution of Cortical Development and Folding Amin S, Borrell V Front Cell Dev Biol 2020 8:604448 https://doi.org/10.3389/fcell.2020.604448
A Retino-retinal Projection Guided by Unc5c Emerged in Species with Retinal Waves Murcia-Belmonte V, Coca Y, Vegar C, Negueruela S, de Juan Romero C, Valiño AJ, Sala S, DaSilva R, Kania A, Borrell V, Martinez LM, Erskine L, Herrera E Current Biology 2019 29(7):1149 https://doi.org/10.1016/j.cub.2019.02.052
Comparison between diffusion MRI tractography and histological tract-tracing of cortico-cortical structural connectivity in the ferret brain Delettre C, Messé A, Dell LA, Foubet O, Heuer K, Larrat B, Meriaux S, Mangin JF, Reillo I, de Juan Romero C, Borrell V, Toro R, Hilgetag CC Network Neurosci 2019 3(4):1038 https://doi.org/10.1162/netn_a_00098
Deconstructing cortical folding: genetic, cellular and mechanical determinants Llinares-Benadero C, Borrell V Nat Rev Neurosci 2019 20(3):161 https://doi.org/10.1038/s41583-018-0112-2
Extensive branching of radially-migrating neurons in the mammalian cerebral cortex Martínez-Martínez MÁ, Ciceri G, Espinós A, Fernández V, Marín O, Borrell V Journal of Comparative Neurology 2019 527(10):1558 https://doi.org/10.1002/cne.24597
Recent advances in understanding neocortical development Borrell V F1000Res 2019 8:F1000 Faculty Rev-1791 https://doi.org/10.12688/f1000research.20332.1
The centrosome protein AKNA regulates neurogenesis via microtubule organization Camargo Ortega G, Falk S, Johansson PA, Peyre E, Broix L, Sahu SK, Hirst W, Schlichthaerle T, De Juan Romero C, Draganova K, Vinopal S, Chinnappa K, Gavranovic A, Karakaya T, Steininger T, Merl-Pham J, Feederle R, Shao W, Shi SH, Hauck SM, Jungmann R, Bradke F, Borrell V, Geerlof A, Reber S, Tiwari VK, Huttner WB, Wilsch-Bräuninger M, Nguyen L, Götz M Nature 2019 567(7746):113 https://doi.org/10.1038/s41586-019-0962-4
Evolution of Cortical Neurogenesis in Amniotes Controlled by Robo Signaling Levels Cardenas A, Villalba A, de Juan Romero C, Pico E, Kyrousi C, Tzika AC, Tessier-Lavigne M, Ma L, Drukker M, Cappello S, Borrell V Cell 2018 174(3):590 https://doi.org/10.1016/j.cell.2018.06.007
How Cells Fold the Cerebral Cortex Borrell V J Neurosci 2018 38(4):776 https://doi.org/10.1523/JNEUROSCI.1106-17.2017
A Complex Code of Extrinsic Influences on Cortical Progenitor Cells of Higher Mammals Reillo I, de Juan Romero C, Cardenas A, Clasca F, Martinez-Martinez MA, Borrell V Cereb Cortex 2017 27(9):4586 https://doi.org/10.1093/cercor/bhx171
Deletion of Dlk2 increases the vulnerability to anxiety-like behaviors and impairs the anxiolytic action of alprazolam Navarrete F, Garcia-Gutierrez MS, Laborda J, Manzanares J Psychoneuroendocrinology 2017 85:134 https://doi.org/10.1016/j.psyneuen.2017.08.015
Regulation of Cerebral Cortex Folding by Controlling Neuronal Migration via FLRT Adhesion Molecules del Toro D, Ruff T, Cederfjaell E, Villalba A, Seyit-Bremer G, Borrell V, Klein R Cell 2017 169(4):621 https://doi.org/10.1016/j.cell.2017.04.012
Skill Learning Modulates RNA Pol II Poising at Immediate Early Genes in the Adult Striatum Galvão-Ferreira P, Lipinski M, Santos F, Barco A, Costa RM eNeuro 2017 4(2):UNSP e0074-17.2017 https://doi.org/10.1523/ENEURO.0074-17.2017
A restricted period for formation of outer subventricular zone defined by Cdh1 and Trnp1 levels Martinez-Martinez Ma, De Juan Romero C, Fernandez V, Cardenas A, Götz M, Borrell V Nat Commun 2016 7:11812 https://doi.org/10.1038/ncomms11812
Cerebral cortex expansion and folding: what have we learned? Fernandez V, Llinares-Benadero C, Borrell V EMBO J 2016 35(10):1021 https://doi.org/10.15252/embj.201593701
Coevolution of radial glial cells and the cerebral cortex De Juan Romero C, Borrell V Glia 2015 63(8):1303 https://doi.org/10.1002/glia.22827
Discrete domains of gene expression in germinal layers distinguish the development of gyrencephaly De Juan Romero C, Bruder C, Tomasello U, Sanz-Anquela JM, Borrell V EMBO J 2015 34(14):1859 https://doi.org/10.15252/embj.201591176
Transcriptional Profiling of Hypoxic Neural Stem Cells Identifies Calcineurin-NFATc4 Signaling as a Major Regulator of Neural Stem Cell Biology Moreno M, Fernandez V, Monllau JM, Borrell V, Lerin C, de la Iglesia N Stem Cell Rep 2015 5(2):157 https://doi.org/10.1016/j.stemcr.2015.06.008
Mechanisms of brain evolution: Regulation of neural progenitor cell diversity and cell cycle length Borrell V, Calegari F Neurosci Res 2014 86:14 https://doi.org/10.1016/j.neures.2014.04.004
Mutations in Eml1 lead to ectopic progenitors and neuronal heterotopia in mouse and human Kielar M, Tuy FPD, Bizzotto S, Lebrand C, De Juan Romero C, Poirier K, Oegema R, Mancini GM, Bahi-Buisson N, Olaso R, LeMoing A, Boutourlinsky K, Boucher D, Carpentier W, Berquin P, Deleuze J, Belvindrah J, Borrell V, Welker E, Chelly J, Croquelois A, Francis F Nat Neurosci 2014 17(7):923 https://doi.org/10.1038/nn.3729
Phenotyping the central nervous system of the embryonic mouse by magnetic resonance microscopy Martinez-Martinez MA, Pacheco-Torres J, Borrell V, Canals S NeuroImage 2014 97:95 https://doi.org/10.1016/j.neuroimage.2014.04.043
Role of Radial Glia cells in cerebral cortex folding Borrell V, Goetz M Curr Opin Neurobiol 2014 27:39 https://doi.org/10.1016/j.conb.2014.02.007
Amplification of progenitors in the mammalian telencephalon includes a new radial glial cell type Pilz GA, Shitamukai A, Reillo I, Pacary E, Schwausch J, Stahl R, Ninkovic J, Snipper HJ, Clevers H, Godinho L,Guillemot F, Borrell V, Matsuzaki F, Goetz M Nat Commun 2013 4:2125 https://doi.org/10.1038/ncomms3125
Contact repulsion controls the dispersion and final distribution of Cajal-Retzius cells Villar-Cerviño V, Molano-Mazon M, Catchpole T, Valdeolmillos M, Henkemeyer M, Martinez LM, Borrell V, Marin O Neuron 2013 77(3):457 https://doi.org/10.1016/j.neuron.2012.11.023
Regulation of cerebral cortex size and folding by expansion of basal progenitors Nonaka-Kinoshita M, Reillo I, Artegiani B, Martinez-Martinez MA, Nelson M, Borrell V, Calegari F EMBO J 2013 32(13):1817 https://doi.org/10.1038/emboj.2013.96
Trnp1 regulates expansion and folding of the mammalian cerebral cortex by control of radial glial fate, Stahl R, Walcher T, De Juan C, Pilz GA, Capello S, Irmler M, Sanz-Anquela JM, Beckers J, Blum R, Borrell V, Gotz M Cell 2013 153(3):535 https://doi.org/10.1016/j.cell.2013.03.027
Abundant Occurrence of Basal Radial Glia in the Subventricular Zone of Embryonic Neocortex of a Lissencephalic Primate, the Common Marmoset Callithrix jacchus Kelava I, Reillo I, Murayama AY, Kalinka AT, Stenzel D, Tomancak P, Matsuzaki F, Lebrand C, Sasaki E, Schwamborn JC, Okano H, Huttner WB, Borrell V Cereb Cortex 2012 22(2):469 https://doi.org/10.1093/cercor/bhr301
Cell-Autonomous Inactivation of the Reelin Pathway Impairs Adult Neurogenesis in the Hippocampus Teixeira CM, Kron MM, Masachs N, Zhang HL, Lagace DC, Martinez A, Reillo I, Duan X, Bosch C, Pujadas L, Brunso L, Song HJ, Eisch AJ, Borrell V, Howell BW, Parent JM, Soriano E J Neurosci 2012 32(35):12051 https://doi.org/10.1523/JNEUROSCI.1857-12.2012
Emerging roles of neural stem cells in cerebral cortex development and evolution Borrell V, Reillo I Dev Neurobiol 2012 72(7):955 https://doi.org/10.1002/dneu.22013
Germinal Zones in the Developing Cerebral Cortex of Ferret: Ontogeny, Cell Cycle Kinetics, and Diversity of Progenitors Reillo I, Borrell V Cereb Cortex 2012 22(9):2039 https://doi.org/10.1093/cercor/bhr284
Slit/Robo Signaling Modulates the Proliferation of Central Nervous System Progenitors Borrell V, Cardenas A, Ciceri G, Galceran J, Flames N, Pla R, Nobrega-Pereira S, Garcia-Frigola C, Peregrin S, Zhao Z, Ma L, Tessier-Lavigne M, Marin O Neuron 2012 76(2):338 https://doi.org/10.1016/j.neuron.2012.08.003
Tau Isoform with Three Microtubule Binding Domains is a Marker of New Axons Generated from the Subgranular Zone in the Hippocampal Dentate Gyrus: Implications for Alzheimer’s Disease Llorens-Martin M, Teixeira CM, Fuster-Matanzo A, Jurado-Arjona J, Borrell V, Soriano E, Avila J, Hernandez F J Alzheimers Dis 2012 29(4):921 https://doi.org/10.3233/JAD-2012-112057
A Role for Intermediate Radial Glia in the Tangential Expansion of the Mammalian Cerebral Cortex Reillo I, De Juan Romero C, Garcia-Cabezas MA, Borrell V Cereb Cortex 2011 21(7):1674 https://doi.org/10.1093/cercor/bhq238
Developmental Sculpting of Dendritic Morphology of Layer 4 Neurons in Visual Cortex: Influence of Retinal Input Callaway EM, Borrell V J Neurosci 2011 31(20):7456 https://doi.org/10.1523/JNEUROSCI.5222-10.2011
Maldevelopment of the cerebral cortex in the surgically induced model of myelomeningocele: implications for fetal neurosurgery Encinas JL, Garcia-Cabezas MA, Barkovich J, Fontecha CG, Peiro JL, Soto GM, Borrell V, Reillo I, Lopez-Santamaria M, Tovar JA, Farmer DL J Pediatr Surg 2011 46(4):713 https://doi.org/10.1016/j.jpedsurg.2010.11.028
In vivo gene delivery to the postnatal ferret cerebral cortex by DNA electroporation Borrell V J Neurosci Methods 2010 186(2):186 https://doi.org/10.1016/j.jneumeth.2009.11.016

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Gene regulatory landscape of cerebral cortex folding

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Multiple parallel cell lineages in the developing mammalian cerebral cortex.

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