Robo3 guides longitudinal axons partially independently of its cytodomain.

Robo3 is an axon guidance receptor that regulates longitudinal axon tract formation in the embryonic ventral nerve cord. Robo3 is thought to guide longitudinal axons by signaling repulsion in response to Slit. To test this, we modified the locus to express a version of the receptor lacking its cytoplasmic domain (Robo3∆C). We find that longitudinal axon guidance is reduced, but not eliminated, in embryos expressing Robo3∆C. Our results show that Robo3's cytodomain is partially dispensable for its axon guidance activity and suggest that it may guide axons via a mechanism other than direct transduction of Slit-dependent signaling.