The contribution of Robos to olfactory sensory axon targeting in the olfactory bulb

Olfactory sensory neurons (OSNs) project a single axon from the olfactory epithelium to the olfactory bulb. OSNs initially target large, distinct, individually identifiable neuropils called protoglomeruli in the zebrafish embryo. Here we examine the contributions Robo axonal guidance receptors make to OSN axon targeting of protoglomeruli. We show that OSNs that project to the DZ protoglomerulus express higher levels of robo2 than those that project to the CZ protoglomerulus, and concordant with this observation, DZ-projecting axons are more often misrouted by loss of robo2 than are CZ-projecting axons. Further, we demonstrate that in the absence of robo2 , robo1 contributes to DZ-targeting but not to CZ-targeting. The loss of either robo1 or robo3 by themselves do not affect targeting to either the CZ or DZ protoglomeruli. These findings identify OSN subtype-dependent contributions of Robo receptors to vertebrate olfactory circuit assembly. In the absence of repellent Slit/Robo signaling, we propose that Netrin1b steers OSN axons to ectopic ventral midline locations where Slit1a and Netrin1b are both expressed.