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Teneurins (Ten) are cell adhesion molecules crucial for neuron migration. This study reveals Ten4 uses a switch between homophilic and Latrophilin interactions to control neuron attachment during cortical development.

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Developmental Biology

Background:

  • Cortical migration is essential for forming functional brain layers.
  • Teneurins (Ten1-4) and Latrophilins (Lphn/ADGRL1-3) are cell adhesion molecules involved in neuronal migration.
  • The integration of homophilic (Ten-Ten) and heterophilic (Ten-Lphn) interactions remains unclear.

Purpose of the Study:

  • To elucidate how Teneurin interactions are integrated during cortical migration.
  • To investigate the structural basis and functional consequences of Ten-Ten and Ten-Lphn binding.
  • To understand the role of Ten4 in orchestrating different stages of neuronal migration.

Main Methods:

  • Single-particle cryo-electron microscopy (cryo-EM) of Ten2.
  • Engineering of surface mutations to disrupt specific Ten interactions.
  • Proteomics, in vivo gene editing, and super-resolution microscopy.

Main Results:

  • Ten2 dimerization is sterically incompatible with Latrophilin binding, indicating exclusive interactions.
  • Engineered mutations disrupting Ten2 interactions are transferable to Ten4, suggesting conserved mechanisms.
  • Ten4 expression increases on migrating neurons; Ten4-Ten4 interactions decrease neuron-RGC attachment in the cortical plate, while Ten4-Lphn interactions promote attachment in the intermediate zone.

Conclusions:

  • Ten4 utilizes a structural/functional switch between homophilic and heterophilic interactions to regulate cortical migration.
  • This switch integrates distinct migration programs by modulating neuron-RGC adhesion at different developmental stages.
  • The findings provide a mechanism for how Teneurins orchestrate complex neuronal migration processes.