Observations on the early development of the optic nerve and tract of the mouse

The early development of the retinofugal pathway of mice has been studied by light and electron microscopic methods in order to define the spatial distribution and the structure of the growth cones as they advance from the eye to the brain. We have studied the relationships of the growth cones to each other, to the glia and, in the older individuals, to the nerve fibers that are already terminating in the brain. We have looked at the rate of advance of the growth cones and have paid particular attention to the changing relationships of the growth cones as they approach the optic chiasm. We have also looked to see whether, at early stages, it is possible to recognise any characteristic features distinguishing the fibers destined to be the thickest in the adult, which come from ganglion cells that are generated among the earliest ganglion cells. In transverse sections through the optic stalk about 50–100 μm behind the eye, the first bundles of fibers are seen on embryonic day 12.5 (E12.5) as a mixture of thin (< 0.5 μm) axons, thicker growth cones, and fine filopodial and foliopodial extensions. During the next two days, as these bundles in the intraorbital nerve increase in size and number, growth cones can be seen in all of the bundles and in all parts of the bundles. They show only a slight preference for one part of the nerve relative to another, and our material provides no evidence for the view that axons are particularly inclined to follow pre‐existing bundles. The structure of the pathway changes significantly as it is traced towards the chiasm, and no section or small stretch of sections can be regarded as representative of the nerve as a whole. As the fibers approach the optic chiasm the growth cones come to lie predominantly close to the pial surface, with the deeper regions occupied almost entirely by fine axons. The change occurs in a region where the glial environment also changes, and where a characteristic neural tube‐like organization first becomes recognizable. Here the glial cells lie in a periventricular position and send slender radial processes out towards the subpial surface. The newly invading axons in the early optic nerve taper from a broad growth cone back to an extremely slender axon, less than 0.5 μm in diameter. The tapered region is of the order of 100–300 μm in length and advances through the nerve at approximately 60 μm per hour. During days 13–19 about 20,000 fibers are added to the nerve each day and by the end of this period almost all of the growth cones have advanced beyond the nerve and tract. All of the axons now have a remarkably uniform, fine caliber, and in the tract there is no indication of the differences that later characterize axons in the different parts of the tract. The fibers destined to be the thickest as yet have no features that distinguish them from the others.