Dephrin, a transmembrane ephrin with a unique structure, prevents interneuronal axons from exiting the Drosophila embryonic CNS.

Ephrin/Eph signalling is crucial for axonal pathfinding in vertebrates and invertebrates. We identified the Drosophila ephrin orthologue, Dephrin, and describe for the first time the role of ephrin/Eph signalling in the embryonic central nervous system (CNS). Dephrin is a transmembrane ephrin with a unique N terminus and an ephrinB-like cytoplasmic tail. Dephrin binds and interacts with DEph, the Drosophila Eph-like receptor, and Dephrin and DEph are confined to different neuronal compartments. Loss of Dephrin or DEph causes the abberant exit of interneuronal axons from the CNS, whereas ectopic expression of Dephrin halts axonal growth. We propose that the longitudinal tracts in the Drosophila CNS are moulded by a repulsive outer border of Dephrin expression.

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