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Structurally Exclusive Teneurin Complexes Orchestrate Divergent Programs in Early Cortical Development

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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Vaishnavi Ravikumar

LAB HEAD: Elena Seiradake

PROVIDER: PXD058769 | Pride | 2026-02-25

REPOSITORIES: Pride

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			Action	DRS
	PEAKS_Results.rar	Other
	QEX03_MF_241108_MBS_TT_102.raw	Raw
	QEX03_MF_241108_MBS_WT_100.raw	Raw
	QEX03_VR_241017_MBS_S3_reinj_085.raw	Raw
	QEX03_VR_241017_MBS_S4_reinj_087.raw	Raw

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