The perinotochordal mesenchyme acts as a barrier to axon advance in the chick embryo: implications for a general mechanism of axonal guidance.

To test the hypothesis that the perinotochordal mesenchyme (the sclerotome ventral to the spinal nerve pathway) is a barrier to axonal advance in the chick embryo, we determined whether axons directly confronted with perinotochordal mesenchyme would turn to avoid it. The initial direction of motor axon outgrowth was altered by rotating the right half of the neural tube after deleting the left half. Perinotochordal mesenchyme was identified histologically or by peanut agglutinin (PNA) binding. We found that axons turned to avoid the perinotochordal mesenchyme and traversed only the dorsal-anterior sclerotome at all stages of outgrowth. When the ventral root was positioned at the midline, axons projected around the perinotochordal mesenchyme and formed spinal nerves on both sides of the embryo. Furthermore, neural crest cells and sensory axons did not penetrate perinotochordal mesenchyme, even in the absence of motor axons. In contrast, perinotochordal mesenchyme did not exhibit inhibitory function and did not differentially bind PNA when the notochord was deleted; axons ramified widely within it. We conclude that the dorsal-anterior sclerotome is permissive and that the perinotochordal mesenchyme is relatively inhibitory for the advance of axons and neural crest cells. Two additional pairs of tissues provide similar permissive/inhibitory contrasts in the embryo, the anterior/posterior sclerotome and the plexus/pelvic girdle mesenchyme. We hypothesize that guidance by all three pairs is mediated by the same set of cellular interactions and has a common molecular basis. We further propose that the transient expression of substances characteristic of these contrasting tissue pairs could serve to guide axons elsewhere, in both the peripheral and the central nervous systems.