Robo1 and Robo2 are homophilic binding molecules that promote axonal growth

In the present study we show that following transfection in 3T3 cells, human Robo1 and Robo2 stimulate neurite outgrowth from Robo-positive neurons (retinal neurons and olfactory neurons), but have no effect on Robo-negative neurons (cerebellar granule cells). The neurite outgrowth response was inhibited by an antibody raised against the first Ig domain of Robo1/2 or by soluble Robo-Fc chimera. Furthermore, we show that the extracellular domains of Robo1 and Robo2 are homophilic adhesion molecules that can also interact with each other. These data suggest a wider range of functions for the Robo family in the development of the nervous system and provide novel insights into the molecular basis for the phenotypes observed in Robo mutants in Drosophila, C. elegans, and zebrafish.