Axonal growth from the habenular nucleus along the neuromere boundary region of the diencephalon is regulated by semaphorin 3F and netrin-1

In neural development, major tracts are often formed along the neuromere boundary regions, although the molecular mechanism underlying this formation remains to be clarified. In the diencephalon, axons from the habenular nucleus extend along the neuromere boundary region between p1 and p2. At embryonic days 13-15, among members of class 3 semaphorins, only semaphorin 3F (Sema3F) was expressed in the diencephalon. Sema3F, which was strongly expressed in the rostral p1, repulsed axons from habenular explants. While p2 explants did not exert a repulsive effect on axons from habenular explants at a distance, habenular axons did not grow into p2 explant. Explants from the ventral region of the caudal diencephalon where netrin-1 is expressed attracted the axons from habenular explants. The attractive effect was blocked by an antibody for DCC. These results suggest that the growth of axons from the habenular nucleus along the neuromere boundary region may be regulated by Sema3F from the rostral p1, and netrin-1 from the ventral region of the caudal diencephalon.