ドラキシン ワ キュウキュウ ト ダイノウ ヒシツ カラ ノ ジクサク セイチョウ オ ネトリン ジュヨウタイ デ アル DCC オ カイシテ ソガイ スル

Olfactory bulb (OB) projection neurons receive sensory input from olfactory receptor neurons and precisely relay it through their axons to the olfactory cortex. Thus, olfactory bulb axonal tracts play an important role in relaying information to the higher order of olfactory structures in the brain. Several classes of axon guidance molecules influence the pathfinding of the olfactory bulb axons. Draxin, a recently identified novel class of repulsive axon guidance protein, is essential for the formation of forebrain commissures and can mediate repulsion of diverse classes of neurons from chickens and mice. In this study, we have investigated the draxin expression pattern in the mouse telencephalon and its guidance functions for OB axonal projection to the telencephalon. We have found that draxin is expressed in the neocortex and septum at E13 and E17.5 when OB projection neurons form the lateral olfactory tract (LOT) rostrocaudally along the ventrolateral side of the telencephalon. Draxin inhibits axonal outgrowth from olfactory bulb explants in vitro and draxin-binding activity in the LOT axons in vivo is detected. The LOT develops normally in draxin-/- mice despite subtle defasciculation in the tract of these mutants. Furthermore, we found that draxin binds specifically and with subnanomolar affinity to the netrin receptor DCC, in a region of DCC distinct from its netrin-binding domain.In vitro, neurites from cortical and olfactory bulb explants of DCC knockout mice show a dramatic reduction in binding of draxin, and their outgrowth is significantly less inhibited by draxin, when compared with neurites from explants of wild type mice. These results unexpectedly identify DCC as a receptor for draxin in axon growth and guidance