Growth cone distribution patterns in the optic nerve of fetal monkeys: implications for mechanisms of axon guidance.
The distribution of growth cones was studied in the optic nerve of monkeys during the first half of prenatal development using quantitative electron microscopic methods. Our aim was to test the hypothesis that ganglion cell growth cones extend predominantly along the surfaces of the nerve, just beneath the pia mater. A complete census of growth cones in cross sections of the nerve during the early phase of axon ingrowth, from embryonic day 39 (E39) to E41, demonstrates that growth cones are scattered within the majority of fascicles, even those located far from the surface of the nerve. By E45, growth cones are concentrated around the nasal, dorsal, and ventral edge of the optic nerve. They are less concentrated in the core and around the temporal edge. However, even as late as E49, virtually all fascicles in the nerve, whether deep or superficial, contain growth cones. Growth cones are dispersed within single fascicles and are often located far from glia. Thus, the newest fibers penetrate deep parts of the pathway and push through centers of densely packed bundles of older axons. This finding is consistent with the vagrant paths of growing axons reported in previous work on embryonic monkey optic nerve (Williams and Rakic, 1985). Our data challenge the hypotheses that growth cones extend selectively along the basal lamina, the pia mater, or glial end feet. Gradients found at later stages of development in the nerve are not due to a particular affinity of growth cones for non-neuronal substrata. The pattern we observed is much more likely to result from central-to-peripheral gradients in ganglion cell generation and possible associations between growth cones originating from the same regions of the retina.
Williams
R W
RW
Section of Neuroanatomy, Yale University School of Medicine, New Haven, Connecticut 06510.
Borodkin
M
M
Rakic
P
P
D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure*; D005314:Embryonic and Fetal Development; D005333:Fetus / Q000033:anatomy & histology*; D000882:Haplorhini / Q000196:embryology; D008854:Microscopy, Electron; D009900:Optic Nerve / Q000196:embryology / Q000648:ultrastructure*; D012165:Retinal Ganglion Cells / Q000648:ultrastructure