The Questions of Developmental Biology

Growth of the retinal ganglion axon to the optic nerve.
The first steps in getting the retinal ganglion
axons to their specific regions of the optic tectum take
place within the retina (Figure 13.28A).
As the retinal ganglion cells differentiate, their
position in the inner margin of the retina is determined
by cadherin molecules (N-cadherin as well as retina-specific R-cadherin) on their cell membranes
(Matsunaga et al. 1988; Inuzuka et al. 1991). The axons from these cells grow along the inner
surface of the retina toward the optic disc, the head of the optic nerve (Figure 13.28B). The
mature human optic nerve will contain over a million retinal ganglion axons. The adhesion and
growth of the retinal cell axons along the inner surface of the retina may be governed by the
laminin-containing basal lamina. However, the attachment to laminin cannot explain the
directionality of this growth. N-CAM appears to be especially important here, since the
directional migration of the retinal ganglion growth cones depends on the N-CAM-expressing
glial endfeet at the inner retinal surface (Stier and Schlosshauer 1995). Also, the secretion of
netrin-1 by the cells of the optic disc (where the axons are assembled from the optic nerve)
probably plays a role in this migration. Mice lacking netrin-1 genes (or the genes for the netrin
receptor found in the retinal ganglion axons) have poorly formed optic nerves, as many of the
axons fail to leave the eye and grow randomly around the disc (Deiner et al. 1997). Condroitin
sulfate proteoglycan, a repulsive factor for retinal neurons, may provide pushes toward the disc
(Hynes and Lander 1992).
Growth of the retinal ganglion axon through the optic chiasm.
When the axons enter the optic nerve, they grow on glial cells toward the midbrain. In nonmammalian
vertebrates, the axons will go to a portion of the brain called the optic tectum.
(Mammalian axons go to the lateral geniculate nuclei; this pathway will be discussed further in
Chapter 21 .) In vitro studies suggest that numerous cell adhesion molecules N-CAM,
cadherins, and integrins play roles in orienting the axon toward the optic tectum (Neugebauer et
al. 1988). Upon their arrival at the optic nerve, the axons fasciculate with axons that are already
present there. N-CAM is critical to this fasciculation, and antibodies against N-CAM (or removal
of its polysialic acid component) cause the axons to enter the optic nerve in a disorderly fashion,
which in turn causes them to emerge at the wrong positions in the tectum (Figure 13.28C; Thanos
et al. 1984; Yin et al. 1995).