The homeodomain transcription factor Hb9 controls axon guidance in Drosophila through the regulation of Robo receptors.

Abstract

Transcription factors establish neural diversity and wiring specificity; however, how they orchestrate changes in cell morphology remains poorly under- stood. The Drosophila Roundabout (Robo) receptors regulate connectivity in the CNS, but how their precise expression domains are established is un- known. Here, we show that the homeodomain tran- scription factor Hb9 acts upstream of Robo2 and Robo3 to regulate axon guidance in the Drosophila embryo. In ventrally projecting motor neurons, hb9 is required for robo2 expression, and restoring Robo2 activity in hb9 mutants rescues motor axon defects. Hb9 requires its conserved repressor domain and functions in parallel with Nkx6 to regu- late robo2 . Moreover, hb9 can regulate the medio- lateral position of axons through robo2 and robo3 , and restoring robo3 expression in hb9 mutants res- cues the lateral position defects of a subset of neu- rons. Altogether, these data identify Robo2 and Robo3 as key effecto