Orientation of commissurai axons in vitro in response to a floor plate- derived chemoattractant

Developing axons are guided to their targets by molecular cues in their local environment. Some cues are shortrange, deriving from cells along axonal pathways. There is also increasing evidence for longer-range guidance cues, in the form of gradients of diffusible chemoattractant molecules, which originate from restricted populations of target cells. The guidance of developing commissurai axons within the spinal cord depends on one of their intermediate cellular targets, the floor plate. We have shown previously that floor plate cells secrete a diffusible factor(s) that can alter the direction of commissurai axon growth in vitro. Here we show that the factor is an effective chemoattractant for commissurai axons. It can diffuse considerable distances through a collagen gel matrix and through dorsal and ventral neural epithelium in vitro to reorient the growth of virtually all commissurai axons. The orientation of axons occurs in the absence of detectable effects on the survival of commissurai neurons or on the rate of commissurai axon extension. The regionally restricted expression of the factor suggests that it is present in the embryonic spinal cord in a gradient with its high point at the floor plate. These observations support the idea that the guidance of commissurai axons to the ventral midline of the spinal cord results in part from the secretion of a chemoattractant by the floor plate.