Effects of fasciculation on the outgrowth of neurites from spinal ganglia in culture.

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Abstract
The influence of neurite fasciculation on the following 2 aspects of nerve growth from chick spinal ganglia in vitro is described: the inhibition of outgrowth by high concentrations of nerve growth factor (NGF) and the preferential growth of neurites toward a capillary tube containing NGF. Cultures of single cells, cell aggregates and intact ganglia were compared and antibodies were used against the nerve cell adhesion molecule (CAM) to perturb fasciculation under a variety of conditions. The inhibition of outgrowth, which was observed with ganglia and aggregates but not with single cells, was correlated with a thickening of neurite fascicles. Anti-CAM, which diminishes fasciculation by inhibiting side-to-side interactions between individual neurites, partially reversed the inhibition of neurite outgrowth at high NGF concentrations. The possibility that neurite bundling causes an increase in the elastic tension of a fascicle without a compensatory increase in its adhesion to substratum was considered. This imbalance could inhibit neurites from growing out from a ganglion and even result in retraction of preexisting outgrowth. In NGF-directed growth a capillary source of NGF produced a steep but transient NGF gradient that subsided before most neurites had emerged from the ganglion. The presence of a single NGF capillary caused a dramatic and persistent asymmetry in the outgrowth of neurites from ganglia or cell aggregates. Processes of individual cells did not appear to orient themselves toward the capillary. Anti-CAM antibodies caused a decrease in the asymmetry of neurite outgrowth. Side-to-side interactions among neurites apparently influence the guidance of nerve bundles by sustaining and amplifying an initial directional signal.