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.


Representative Publications

Cárdenas A. , Villalba A, De Juan Romero C, Picó E, Kyrousi C, Tzika AC, Tessier-Lavigne M, Ma L, Drukker M, Cappello S, Borrell V. " Evolution of cortical neurogenesis in amniotes controlled by Robo signaling levels. " Cell . 174 , 590 - 606.e21 ( 2018 )

Del Toro D , Ruff T, Cederfjäll E, Villalba A, Seyit-Bremer G, Borrell V, Klein R " Regulation of cerebral cortex folding by controlling neuronal migration via FLRT adhesion molecules. " Cell . 169 , 621 - 635 ( 2017 )

Fernández V , Llinares-Benadero C, Borrell V " Cerebral cortex expansion and folding: what have we learned? " EMBO J . 35 , 1021 - 1044 ( 2016 )

Martínez-Martínez M , De Juan Romero C, Fernández V, Cárdenas A, Götz M, Borrell V " A restricted period for formation of outer subventricular zone defined by Cdh1 and Trnp1 levels. " Nat Comm . 7 , - 11812 ( 2016 )

De Juan Romero C , Bruder C, Tomasello U, Sanz-Anquela JM and Borrell V. " Discrete domains of gene expression in germinal layers distinguish the development of gyrencephaly " EMBO Journal (Cover caption) . 34(14) , 1859 - 1874 ( 2015 )