Structurally exclusive Teneurin complexes orchestrate divergent programs in early cortical development

Journal article

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.

Authors: Berbeira-Santana, M; Peregrina, C; Okuda, K; Zhou, JC; Carrasquero-Ordaz, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Communications
• Volume: 17
• Issue: 1
• Article number: 5292
• Publication date: 2026-04-16
• Acceptance date: 2026-03-24
• DOI: 10.1038/s41467-026-71619-1
• EISSN: 2041-1723
• ISSN: 2041-1723
• Language: English
• Keywords: Process (computing); Cell adhesion; Cell migration; Cell adhesion molecule; Mammalian brain; Plasma protein binding; Nerve net; Cell lineage