Temporal regulation of growth cone lamellar protrusion and the influence of target tissue.

Guided nerve fiber growth depends upon the activities of the neuronal growth cone lamellae and filopodia. Defining the dynamics of growth cone remodeling and the influences that act on it may lead to greater understanding of guided axonal growth. While there were differences in the remodeling of growth cones of nerve fibers extended from spinal cord explants and from dorsal root ganglia of Rana pipiens larvae, both types exhibited fluctuations in lamellar expanse over time to produce "lamellar cycles." We now show that these cycles are characterized by the temporal regulation of lamellar protrusion rate, the percentage of the lamellar perimeter undergoing protrusion, and invariant lamellar retraction with respect to time. Since axotomies did not abolish the lamellar cycles, the mechanism underlying cycling appears to reside at the level of the nerve fiber terminus. The previously demonstrated effects of the target tissue on growth cone remodeling appear to be due to target tissue-released factors that bind to the culture substratum, as evidenced by experiments using target tissue-conditioned medium. Further, the target tissue attenuated the fluctuations in lamellar protrusion rate during cycling, which resulted in changes in growth cone remodeling and morphology. These alterations may be related to the chemokinetic and chemotropic effects of the target on the nerve fiber extension. Thus, the process of remodeling of growth cone lamellar structures is the result of intrinsically controlled modifications in lamellar protrusion and target-based influences.