During development, neuronal circuits are organized by various molecules. In the olfactory circuit, the axons emerging from the olfactory bulb (OB) form their fasciculate bundles termed lateral olfactory tract (LOT), and their collateral branches thereafter. We discovered LOT usher substance (LOTUS) as a novel protein that contributes to LOT formation through blockade of the binding of Nogo-A, an axonal growth inhibitor, to Nogo receptor-1 (NgR1). Furthermore, we found that up-regulation of Nogo-A in the LOT sprouts collateral branching of the LOT by overcoming the antagonism for NgR1 by LOTUS. In this review, we focus on the novel roles of Nogo-A, NgR1 and LOTUS in axonal bundling and branching of the LOT, and discuss the possible involvement of the molecular mechanisms regulated by these proteins in the development of other neuronal networks.
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