DCC plays a role in navigation of forebrain axons across the ventral midbrain commissure in embryonic Xenopus

In the developing vertebrate brain, growing axons establish a scaffold of a xon tracts connected across the midline via commissures. We have previously identified a population of telencephalic neurons that express NOC-2, a nov el glycoform of the neural cell adhesion molecule N-CAM that is involved in axon guidance in the forebrain. These axons arise from the presumptive tel encephalic nucleus, course caudally along the principal longitudinal tract of the forebrain, cross the ventral midline in the midbrain, and then proje ct to the contralateral side of the brain. In the present study we have inv estigated mechanisms controlling the growth of these axons across the ventr al midline of the midbrain. The axon guidance receptor DCC is expressed by the NOC-2 population of axons both within the longitudinal tract and within the ventral midbrain commissure. Disruption of DCC-dependent interactions, both in vitro and in vivo, inhibited the NOC-2 axons from crossing the ven tral midbrain. Instead, these axons grew along aberrant trajectories away f rom the midline, suggesting that DCC-dependent interactions are important f or overcoming inhibitory mechanisms within the midbrain of the embryonic ve rtebrate brain. Thus, coordinated responsiveness of forebrain axons to both chemostimulatory and chemorepulsive cues appears to determine whether they cross the ventral midline in the midbrain, (C) 2000 Academic Press.