RETINAL AXON DIVERGENCE IN THE OPTIC CHIASM - DYNAMICS OF GROWTH CONEBEHAVIOR AT THE MIDLINE

To study how retinal ganglion cell axons diverge in the optic chiasm, the behavior of dye-labeled fibers was monitored in real time with vid eo microscopy in an isolated preparation of embryonic mouse brain, wit h a focus on embryonic day 15-16. These real-time studies have reveale d the dynamics of the growth of individual retinal axons, especially t he tempo of extension and growth cone behaviors during divergence in t he chiasm, a model for ''decision'' regions in developing pathways. Wi thin the chiasm, retinal growth cones extend by saltatory growth, cons isting of bursts of rapid advance alternating with pauses in extension . During pauses, growth cone appendages remain; motile, and develop as ymmetries prior to a change in the axis of growth. In a zone straddlin g the midline, retinal fibers, irrespective of destination, display lo ng pauses for up to several hours, making small advances and retractio ns with no net extension. While crossed fibers ultimately progress thr ough the midline, uncrossed fibers from inferior temporal retina devel op wide-ranging branched growth cones, and then turn back to the ipsil ateral side. Turns are effected by the selective retraction or micropr uning of asymmetric foci of motile activity, and by the transformation of a backward-directed filopodium into a new growth cone. The behavio r of retinal axons at the midline supports the hypothesis that this lo cus contains cues important for retinal axon divergence. Moreover, the observations of growth cone kinetics in the chiasm elucidate which gr owth cone forms seen in static preparations mediate growth cone turnin g, and suggest a model of axon navigation in decision regions in the i ntact nervous system.