Lakhina, V., Marcaccio, C.L., Shao, X., Lush, M.E., Jain, R.A., Fujimoto, E., Bonkowsky, J.L., Granato, M., and Raper, J.A. (2012) Netrin/DCC Signaling Guides Olfactory Sensory Axons to Their Correct Location in the Olfactory Bulb. The Journal of neuroscience : the official journal of the Society for Neuroscience. 32(13):4440-4456.
Olfactory sensory neurons expressing particular olfactory receptors project to specific reproducible locations within the
bulb. The axonal guidance cues that organize this precise projection pattern are only beginning to be identified. To aid in
their identification and characterization, we generated a transgenic zebrafish line, OR111-7:IRES:Gal4, in which a small subset
of olfactory sensory neurons is labeled. Most sensory neurons expressing the OR111-7 transgene project to a specific location within the bulb, the central zone protoglomerulus, while a smaller number project
to the lateral glomerulus 1 protoglomerulus. Inhibiting Netrin/DCC (deleted in colorectal cancer) signaling perturbs the ability
of OR111-7-expressing axons to enter the olfactory bulb and alters their patterns of termination within the bulb. The Netrin
receptor DCC is expressed in olfactory sensory neurons around the time that they elaborate their axons, netrin1a is expressed
near the medial-most margin of the olfactory bulb, and netrin1b is expressed within the ventral region of the bulb. Loss of
Netrin/DCC signaling components causes some OR111-7-expressing sensory axons to wander posteriorly after exiting the olfactory
pit, away from netrin-expressing areas in the bulb. OR111-7-expressing axons that enter the bulb target the central zone less
precisely than normal, spreading away from netrin-expressing regions. These pathfinding errors can be corrected by the reexpression
of DCC within OR111-7 transgene-expressing neurons in DCC morphant embryos. These findings implicate Netrins as the only known attractants for
olfactory sensory neurons, first drawing OR111-7-expressing axons into the bulb and then into the ventromedially positioned
central zone protoglomerulus.