Neurite extension across regions of low cell-substratum adhesivity: implications for the guidepost hypothesis of axonal pathfinding.

According to the adhesive "guidepost" hypothesis, pioneer axons follow pathways marked by specific nonadjacent cells (guidepost cells). The hypothesis implies that high adhesivity between extending axons and guidepost cells facilitates axon extension across low-adhesivity tissues or spaces between guidepost cells. This study investigates the ability of a high-adhesivity substratum to promote axonal extension across a low-adhesivity substratum in vitro. Dissociated chick embryo dorsal root ganglion neurons are cultured on a substratum consisting of areas of high-adhesivity substratum-bound laminin (i.e., model adhesive guideposts) separated by a low-adhesivity agarose substratum. Increasing the cell-substratum adhesivity of these guideposts results in an increase in the percentage of neurites spanning a given width of the low-adhesivity substratum. Filopodial processes at the tips of neurites can extend over the low-adhesivity substratum. Apparently, filopodial contact with high-adhesivity guideposts enables neurites to extend across intervening low-adhesivity substrata. The maximum width of low-adhesivity substratum discontinuities spanned by some neurites in vitro is comparable to the distance between some putative guidepost cells in insects. Consistent with the adhesive guidepost hypothesis, these findings demonstrate neurite extension on a substratum of discontinuous cell-substratum adhesivity.