Expression and putative role of neuropilin-1 in the early scaffold of axontracts in embryonic Xenopus brain

Although the general principles of axon guidance in vitro are understood, l ittle is known about how axons respond to the myriad of cues in vivo and na vigate axon pathways within the complex milieu of the embryonic brain. Alth ough neuropilin-1 is an axon guidance receptor for chemorepulsive ligands i n the class 3 subfamily of semaphorins, its role in directing axon growth i n vivo is unknown. In the present study, we have examined the expression an d role of neuropilin-1 in the embryonic forebrain of Xenopus. Neuropilin-1 was selectively expressed by a subset of axons in the early scaffold of axo n tracts. These axons arise from the presumptive telencephalic nucleus, cro ss the rostral midline by means of the postoptic commissure, and enter the major longitudinal tract of the prosencephalon, the tract of the postoptic commissure. At the level of the mesencephalon, these axons diverge and ente r one of two axon tracts: either the ventral longitudinal tract or the vent ral commissure. This same population of axons also expresses NOC-2, a novel glycoform of the neural cell adhesion molecule N-CAM. We have previously r evealed the presence of a chemorepulsive activity underlying the pathway fo llowed by these axons as they cross the ventral commissure. When neuropilin -1 was overexpressed after blastomere injections of synthetic RNA transcrip ts, NOC-2 axons entered the ventral commissure but failed to cross the midl ine. Instead, these axons were inhibited from growing ventrally within the commissural pathway. These results suggest that the level of neuropilin-1 i n the NOC-2 subpopulation of axons is critical for determining whether thes e axons reach the ventral midline. Thus, neuropilin-1 may a specific role i n directing the growth of NOC-2 axons across the ventral midline in the ear ly embryonic mesencephalon. (C) 2000 Wiley-Liss, Inc.