THE GUIDANCE MOLECULE SEMAPHORIN-III IS EXPRESSED IN REGIONS OF SPINAL-CORD AND PERIPHERY AVOIDED BY GROWING SENSORY AXONS

The protein collapsin was purified from chick brain on the basis of it s ability to inhibit sensory neuron growth cones, implicating this mol ecule in sensory axon guidance (Luo et al. [1993] Cell 75:217-227). To examine the relationship between collapsin and sensory axon growth, w e examined the pattern of mRNA expression of collapsin's mammalian par alogue, Semaphorin III (Sema III), and compared it to dorsal root gang lion (DRG) axon pathways in the developing rat embryo. Centrally, DRG axons enter the spinal cord by embryonic (E) 11 and branch into the gr ay matter by E15 in brachial and thoracic regions. Laminar specific ta rgets are reached by E17. Between E13 and E17, Sema III mRNA is expres sed at high levels in the entire ventral half of the spinal cord excep t the floor plate. This pattern suggests that Sema III may inhibit non -proprioceptive sensory axons from penetrating the ventral spinal cord . Peripherally, sensory axons have entered the anterior sclerotome by E11 at all rostrocaudal levels. At this age, Sema III mRNA is already expressed in the dermamyotome and ventral aspect of the posterior scle rotome, areas which axons pass between but do not penetrate en route t o their peripheral targets. From E12 to E15, the axons lengthen and br anch into smaller fascicles which extend toward peripheral targets. Du ring this time, Sema III mRNA is expressed by many mesodermal structur es surrounding the axon fascicles, with highest levels observed in the dermamyotome, perinotochordal mesenchyme, pelvic girdle, and limb. As development proceeds, Sema III mRNA expression is quickly downregulat ed before disappearing by birth. Taken together, our results demonstra te that the gene for Sema III is expressed in central and peripheral r egions which are avoided by growing DRG axons. These findings are cons istent with the idea that Sema III inhibits growth and branching of ax ons into inappropriate areas during development. (C) 1995 Wiley-Liss, Inc.