Cortical neurodevelopment. PI: Daniel Del Toro Ruiz


The neocortex is the most evolutionarily region of the brain and the source of high cognitive skills such as language. During development, two coordinated events shape its morphology, leading to the cortex’s columnar and layered structure: the proliferation of neuronal progenitors and cortical migration. The focus of our laboratory is to understand how these two processes also contribute to the expansion and folding of the cerebral cortex. We use expression profiling experiments, conditional mouse lines, functional in vitro and in vivo assays together with advanced imaging techniques to determine molecular mechanisms involved in cortex folding. We are currently interested in examining the role of synaptic proteins during cortical migration and the impact of cortex folding on animal behaviour and intelligence.

KEYWORDS: proliferation, migration, reprogramming, cortex

Daniel del Toro Ruiz
Postdoctoral researcher Ramón y Cajal


Claudia Peregrina Cabredo
Predoctoral researcher
Institut de Neurociències


Sofía Zaballa Larrinaga
Predoctoral researcher

  • Neuronal migration and proliferation mechanisms leading to folding of the cerebral cortex.



  • Molecular mechanisms involved in lateral dispersion of cortical neurons.
  • Impact of neuronal migration and proliferation on cortex folding.
  • Induction of cortex folding in animals that normally have a smooth cortex such as mice.

  • Novel mechanisms of neuronal migration leading to cortex folding

Project reference: RTI2018-095580-A-I00
PI: Daniel del Toro Ruiz
Affiliation entity: Universitat de Barcelona
Funding entity: Ministerio de Ciencia y Educación
Period: 2019-2021
Amount: 145.000 €

  • Ramon y Cajal Project

Project reference: RYC-2017-23486
PI: Daniel del Toro Ruiz
Affiliation entity: Universitat de Barcelona
Funding entity: Programa Ramon y Cajal
Period: 2019-2024
Amount: 40.000 €

  • In vivo reprogramming to rescue alterations in Huntington’s disease

Project reference: ... ...
Group member. PI: Josep M. Canals Coll
Affiliation entity: Universitat de Barcelona
Funding entity: Fundació "La Caixa"
Period: 2022-2024
Amount: 994.890 €

For more information for PI publications click in the link:
ORCID: 0000-0002-7416-2155

Fleitas C, Marfull-Oromí P, Chauhan D, Del Toro D, Peguera B, Zammou B, Rocandio D, Klein R, Espinet C, Egea J. FLRT2 and FLRT3 Cooperate in Maintaining the Tangential Migratory Streams of Cortical Interneurons during Development. J Neurosci. 2021 Sep 1;41(35): 7350-7362. doi: 10.1523/ JNEUROSCI. 0380-20.2021. Epub 2021 Jul 23. PubMed. PMID: 34301831.

Peregrina C, Del Toro D. FLRTing Neurons in Cortical Migration During Cerebral Cortex Development. Front Cell Dev Biol. 2020;8:578506. doi: 10.3389/ fcell.2020. 578506. eCollection 2020. Review. PMID: 33043013.

Del Toro D*, Carrasquero-Ordaz MA*, Chu A*, Ruff T, Shahin M, Jackson VA, Chavent M, Berbeira-Santana M, Seyit-Bremer G, Brignani S, Kaufmann R, Lowe E, Klein R and Seiradake E. Structural Basis of Teneurin-Latrophilin Interaction in Repulsive Guidance of Migrating Neurons. Cell. 2020 Jan 23;180(2): 323-339.e19. doi: 10.1016/ j.cell.2019.12.014. Epub 2020 Jan 99. *Equal contribution. PMID: 31928845.

del Toro D*, Ruff T*, Cederfjall E, Villalba A, Seyit-Bremer G, Borrell V and Klein R. Regulation of cerebral cortex folding by controlling neuronal migration via FLRT adhesion molecules. Cell. 2017 May 4;169(4): 621-635.e16. doi: 10.1016/ j.cell.2017.04.012. *Equal contribution. PMID: 28475893.

Jackson VA, Mehmood S, Chavent M, Roversi P, Carrasquero M, del Toro D, Seyit-Bremer G, Ranaivoson FM, Comoletti D, Sansom MS, Robinson CV, Klein R, Seiradake E. Super-complexes of adhesion GPCRs and neural guidance receptors. Nat Commun. 2016 Apr 19;7:11184. doi: 10.1038/ ncomms11184. PMID: 27091502.

Jackson VA, del Toro D, Carrasquero M, Roversi P, Harlos K, Klein R, Seiradake E. Structural basis of latrophilin-FLRT interaction. Structure 2015 Apr 7;23(4): 774-81. doi: 10.1016/ j.str.2015.01.013. Epub 2015 Feb 26. PMID: 25728924.

Seiradake E*, del Toro D*, Nagel D, Cop F, Härtl R, Ruff T, Seyit-Bremer G, Harlos K, Border EC, Acker-Palmer A, Jones EY, Klein R. FLRT structure: balancing repulsion and cell adhesion in cortical and vascular development. Neuron. 2014 Oct 22;84(2): 370-85. doi: 10.1016/ j.neuron.2014.10.008. Epub 2014 Oct 22. *Equal contribution. PMID: 25374360.

Leyva-Díaz E, del Toro D, Menal MJ, Cambray S, Susín R, Tessier-Lavigne M, Klein R, Egea J, López-Bendito G. FLRT3 is a Robo1-interacting protein that determines Netrin-1 attraction in developing axons. Curr. Biol. 2014 Mar 3;24(5): 494-508. doi: 10.1016/ j.cub.2014.01.042. Epub 2014 Feb 20. PMID: 24560577.

Brito V, Puigdellívol M, Giralt A, del Toro D, Alberch J, Ginés S. Imbalance of p75(NTR)/TrkB protein expression in Huntington's disease: implication for neuroprotective therapies. Cell Death Dis. 2013 Apr 18;4(4): e595. doi: 10.1038/ cddis.2013.116. PMID: 23598407.

Seiradake E, Schaupp A, del Toro D, Kaufmann R, Mitakidis N, Harlos K, Aricescu AR, Klein R, Jones EY. Structurally encoded intraclass differences in EphA clusters drive distinct cell responses. Nat Struct Mol Biol. 2013 Aug;20(8): 958-64. doi: 10.1038/ nsmb.2617. Epub 2013 Jun 30. PMID: 23812375.

Yamagishi S, Hampel F, Hata K, del Toro D, Schwark M, Kvachnina E, Bastmeyer M, Yamashita T, Tarabykin V, Klein R, Egea J. FLRT2 and FLRT3 act as repulsive guidance cues for Unc5-positive neurons. EMBO J. 2011 Jun 14;30(14): 2920-33. doi: 10.1038/ emboj.2011.189. PMID: 21673655.

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