In the vertebrate nervous system, sensory information is spatially encoded in the brain, forming topographic maps that are fundamental for cognition and higher-order processing of sensory information. Mechanisms of topographic axon wiring have been long-standing questions in neuroscience. It has been thought that the topography of the neural map is determined by graded positional cues that are expressed by the target (model A). However, here we found that pre-target axon sorting is important for the topographic map formation in the mouse olfactory system (model B). In olfactory sensory neurons, an axon guidance receptor, Neuropilin-1 and its repulsive ligand, Semaphorin-3A are expressed in a complementary manner. Expression levels of Neuropilin-1 determined both pre-target sorting and projection sites of axons. Olfactory sensory neuron-specific knockout of Semaphorin-3A perturbed axon sorting and altered the olfactory map topography. Thus, pre-target axon sorting plays an important role in establishing the topographic order based on the relative levels of guidance molecules expressed by axons. The axon-axon interaction may be a general strategy to establish the topographic order based on the relative levels of guidance molecules expressed by axons.

Science (Research Article), published online, July 9, 2009.
"Pre-Target Axon Sorting Establishes the Neural Map Topography"
Takeshi Imai, Takahiro Yamazaki, Reiko Kobayakawa, Ko Kobayakawa, Takaya Abe, Misao Suzuki, and Hitoshi Sakano