Lines of investigation
Our lab is interested in understanding the cellular and molecular mechanisms governing the expansion of the cerebral cortex observed across mammalian evolution. The cerebral cortex is the largest structure in the brain and is responsible, among others, for the higher cognitive functions that distinguish humans from other mammals. The extraordinary growth in the size of the cerebral cortex observed across the mammalian evolutionary scale is thought to underlie the concomitant growth in intellectual capacity. This evolutionary expansion of the cerebral cortex is recapitulated during development in higher mammals, when the embryonic cerebral cortex undergoes massive growth in surface area, and folds itself in stereotypic patterns.
In recent years multiple genetic mutations have been identified as the leading cause for mental retardation or impairment of intellectual capacity in humans. These mutations have been consistently linked to defects of cortical development during embryogenesis, and functional studies in rodents have shown that these genes play essential roles in distinct aspects of cortical neuron migration or of cortical folding.
We are interested in the identification and analysis of the basic mechanisms involved in the normal expansion and folding of the cerebral cortex in higher mammals. To study this we combine genetic tools (in vitro and in vivo electroporation, viral vectors, transgenic and knock-out mice), experimental embryology, state-of-the-art imaging techniques and standard histological, cellular and molecular biology methods, using various species as experimental models. Currently, our efforts are focused on understanding the role of Cajal-Retzius cells and intermediate progenitors in the tangential vs. radial expansion of the cerebral cortex, and in the formation of gyri at stereotypic locations in the cerebral cortex during development.
- 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
- 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
- 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
- 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
- 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