F-spondin is a contact-repellent molecule for embryonic motor neurons

The floor plate plays a key role in patterning axonal trajectory in the emb ryonic spinal cord by providing both long-range and local guidance cues tha t promote or inhibit axonal growth toward and across the ventral midline of the spinal cord, thus acting as an intermediate target for a number of cro ssing (commissural) and noncrossing (motor) axons. F-spondin, a secreted ad hesion molecule expressed in the embryonic floor plate and the caudal somit e of birds, plays a dual role in patterning the nervous system. It promotes adhesion and outgrowth of commissural axons and inhibits adhesion of neura l crest cells. In the current study, we demonstrate that outgrowth of embry onic motor axons also is inhibited by F-spondin protein in a contact-repuls ion fashion. Three independent lines of evidence support our hypothesis: su bstrate-attached F-spondin inhibits outgrowth of dissociated motor neurons in an outgrowth assay; F-spondin elicits acute growth cone collapse when ap plied to cultured motor neurons; and challenging ventral spinal cord explan ts with aggregates of HEK 293 cells expressing F-spondin, causes contact-re pulsion of motor neurites. Structural-functional studies demonstrate that t he processed carboxyl-half protein that contains the thrombospondin type 1 repeats is more prominent in inhibiting outgrowth, suggesting that the proc essing of F-spondin is important for enhancing its inhibitory activity.