F-spondin is a contact-repell4 embryonic motor neurons

The floor plate plays a key role in patterning axonal trajectory in F the embryonic spinal cord by providing both long-range and local at guidance cues that promote or inhibit axonal growth toward and m across the ventral midline of the spinal cord, thus acting as an sc intermediate target for a number of crossing (commissural) and ar noncrossing (motor) axons. F-spondin, a secreted adhesion molela cule expressed in the embryonic floor plate and the caudal somite re of birds, plays a dual role in patterning the nervous system. It th promotes adhesion and outgrowth of commissural axons and m inhibits adhesion of neural crest cells. In the current study, we demonstrate that outgrowth of embryonic motor axons also is er inhibited by F-spondin protein in a contact-repulsion fashion. Three in independent lines of evidence support our hypothesis: substrateat attached F-spondin inhibits outgrowth of dissociated motor neunc rons in an outgrowth assay; F-spondin elicits acute growth cone cc collapse when applied to cultured motor neurons; and challenging cl ventral spinal cord explants with aggregates of HEK 293 cells 2' expressing F-spondin, causes contact-repulsion of motor neurites. m Structural-functional studies demonstrate that the processed p; carboxyl-half protein that contains the thrombospondin type 1 ot repeats is more prominent in inhibiting outgrowth, suggesting m that the processing of F-spondin is important for enhancing its inhibitory activity. Dl