Structurally exclusive Teneurin complexes orchestrate divergent programs in early cortical development.

Overview

1. Department of Biochemistry, University of Oxford,Oxford, UK
2. Kavli Institute for Nanoscience Discovery, University of Oxford,Oxford, UK
3. Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Institute of Neurosciences, IDIBAPS, CIBERNED, University of Barcelona,Barcelona, Spain
4. Interdisciplinary Institute for Neuroscience, CNRS UMR 5297 and University of Bordeaux,Bordeaux, France
5. Institut für Anatomie und Zellbiologie, Universitätsmedizin Göttingen,Göttingen, Germany
6. Laboratoire de Microbiologie et Génétique Moléculaires, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS,Toulouse, France
7. Diamond Light Source, Harwell Science and Innovation Campus,Didcot, UK
8. Department of Biology, Howard Hughes Medical Institute, Stanford University,Stanford, CA USA
9. Structural Biology Brussels, Vrije Universiteit Brussel (VUB),Brussels, Belgium
10. VIB-VUB Centre for Structural Biology, VIB,Brussels, Belgium

Abstract

Cortical migration is a complex process in which neurons migrate along radial glial cells (RGC) to form functional layers. Teneurins (Ten1-4) play a role by interacting with Latrophilins (Lphn/ADGRL1-3). Teneurins are also known as cell adhesion molecules, but how homophilic and heterophilic Teneurin interactions are integrated is unknown. Here, single-particle-cryo-EM data of Ten2 shows that canonical Latrophilin-binding is sterically incompatible with Ten2-dimerisation, making these interactions exclusive. We engineered surface mutations that specifically disrupt Ten2-Ten2 or Ten2-Latrophilin interactions. These are transferrable to Ten4, suggesting conserved binding mechanisms. Proteomics, in-vivo-gene-editing and super-resolution-microscopy show that Ten4 is expressed along RGC fibres and that migrating neurons switch from low-to-high Ten4-expression. Ten4 expression is highest in the cortical plate where Ten4-Ten4 interactions reduce RGC-attachment. In the intermediate zone, Ten4-Latrophilin interactions are required to promote neuron-RGC association. The results show how Ten4 orchestrates different stages of cortical migration by using a structural/functional switch between high-affinity Lphn interactions and low-affinity homophilic interactions, underpinning the integration of distinct migration programmes.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

Code availability

The scripts and macros used for quantification of the stripe assays or cell binding assays can be made available upon request to the lead contacts Daniel del Toro and Elena Seiradake.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• ebi.ac.uk/emdb/emd-50975, at EMBL-EBI; found in “Data availability”
• ebi.ac.uk/emdb/emd-50976, at EMBL-EBI; found in “Data availability”
• ebi.ac.uk/emdb/emd-51021, at EMBL-EBI; found in “Data availability”
• ebi.ac.uk/emdb/emd-51022, at EMBL-EBI; found in “Data availability”
• geo:GSE153164, at NCBI GEO; found in “Data availability”
• pride:PXD058769, at PRIDE; found in “Data availability”

Data availability

The electron density maps for the mouse Ten2 dimers have been deposited in the Electron Microscopy Data Bank under the accession codes: EMD-51022 (A0B0) (https://www.ebi.ac.uk/emdb/EMD-51022), EMD-50975 (A1B1) (https://www.ebi.ac.uk/emdb/EMD-50975), EMD-50976 (A1BO) (https://www.ebi.ac.uk/emdb/EMD-50976), and EMD-51021 (A0B1) (https://www.ebi.ac.uk/emdb/EMD-51021). The atomic coordinates and models resulting from the structural analysis of the aforementioned maps have been deposited on the Protein Data Bank under the following accession codes, respectively: 9G42 (A0B0) (10.2210/pdb9G42/pdb), 9G2F (A1B1) (10.2210/pdb9G2F/pdb), 9G2H (A1B0) (10.2210/pdb9G2H/pdb), and 9G41 (A0B1) (10.2210/pdb9G41/pdb). The mass spectrometry data of the Teneurin mutants can be found in ProteomeXchange under the accession code: PXD058769 (https://www.ebi.ac.uk/pride/archive/projects/PXD058769). The tissue mass spectrometry data of the different cortical layers can be found in the PRIDE repository under the accession code: PXD075073 (https://www.ebi.ac.uk/pride/archive/projects/PDX075073). The Teneurin3 and 4 dimers shown in Supplementary Fig. 1 are available in the PDB: 8R50 (10.2210/pdb8R50/pdb) and 7BAM (10.2210/pdb7BAM/pdb). Single-cell RNA-seq data is available in NCBI GEO: GSE153164 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE153164) and GSE271794 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE271794). Molecular dynamics trajectories are available upon request. Unedited Western blots are shown in the Supplementary Information File. Source data are provided with this paper.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 17 authors, 2 keywords, 13 MeSH terms, 1 funder, 124 references, 5 RRIDs.

Cite

This paper

Berbeira-Santana, M., Peregrina, C., Okuda, K., Zhou, J. C., Carrasquero-Ordaz, M., Roberts, A. V., Thomas, A. E., Haanappel, E., Chavent, M., el Omari, K., Baker, L. A., Pederick, D. T., Pardon, E., Steyaert, J., Nägerl, U. V., del Toro, D., & Seiradake, E. (2026). Structurally exclusive Teneurin complexes orchestrate divergent programs in early cortical development. Nature communications, 17(1), 5292. https://doi.org/10.1038/s41467-026-71619-1

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