A balance between positive and negative signals determines whether axons cross the midline of the spinal cord

Commissural axons located in the dorsolateral spinal cord extend their axons toward the ventral midline, the floor plate. Axons enter the floor plate to cross the midline. Once they reach the contralateral floor-plate border they turn rostrally into the longitudinal axis. Because of the easy read-out (crossing versus non-crossing of the midline) commissural axons have been the favorite model system for a large number of axon pathfinding studies.

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We have identified a number of guidance cues that help axons find their way to and across the floor plate. The bottom line of these studies is the model of a balance between positive and negative signals that determines the behavior of axons at the midline. Commissural axons, i.e. axon that cross the midline, are attracted toward and into the floor plate, because they experience a predominance of positive signals derived

from molecular interactions between the receptors on their surface and the guidance cues expressed by the floor-plate cells. The contact with the floor plate induces a change in protein expression in the neuron resulting in the insertion of new receptors at the axon tip. These new receptors sense additional guidance cues that are repellents. Thus, the initially positive balance is shifted to more and more negative signals causing ultimately the expulsion of axon from the floor plate on the contralateral side. The same model explains the behavior of non-crossing axons at the floor plate: In contrast to crossing axons, the non-crossing axons express high levels of the receptors for the midline-derived repellents from the start. Therefore they will not invade the floor plate, and hence, not cross the midline.
          

Publications:

   
Pekarik, V., Bourikas, D., Miglino, N., Joset, P., Preiswerk, S., and Stoeckli, E.T. (2003) Screening for gene function in chicken embryo using RNAi and electroporation Nat. Biotechnol., 21: 93-96    pubmed
Zou, Y., Stoeckli, E., Chen, H., Brose, K., and Tessier-Lavigne, M. (2000) Squeezing axons out of the gray matter: A role for slit and semaphorin proteins from midline and ventral spinal cord Cell, 102: 363-375    pubmed
Burstyn-Cohen T., Tzarfaty, V., Frumkin, A., Feinstein, Y., Stoeckli, E.T., and Klar, A. (1999) F-spondin is required for accurate pathfinding of commissural axons at the floor plate Neuron, 23: 233-246    pubmed
Stoeckli, E.T., and Landmesser, L.T. (1998) Axon guidance at choice points Curr. Opin. Neurobiol., 8: 73-79    pubmed
Stoeckli, E.T., Sonderegger, P., Pollerberg, G.E., Landmesser, L.T. (1997) Interference with axonin-1 and NrCAM interactions unmasks a floor plate activity inhibitory for commissural axons Neuron, 18: 209-221    pubmed
Stoeckli, E.T., and Landmesser, L.T. (1995) Axonin-1, NrCAM, and NgCAM play different roles in the in vivo guidance of chick commissural neurons Neuron, 14: 1165-1179    pubmed