New views on retinal axon development: a navigation guide

Abstract

The eye is a peripheral outpost of the central nervous system (CNS) where the retinal ganglion cells (RGCs) reside. RGC axons navigate to their targets in a remarkably stereotyped and error-free manner and it is this process of directed growth that underlies the complex organization of the adult brain. The RGCs are the only retinal neurons to project into the brain and their peripheral location makes them an unusually accessible population of projection neurons for experiments involving in vivo gene transfer, anatomical tracing, transplantation and in vitro culture. In this paper, we review recent findings that have contributed to our understanding of some of the guidance decisions that axons make in the developing visual system. We look at two choice points in the pathway, the optic nerve head (onh) and the midline chiasm, and discuss evidence that supports the idea that key molecules in guiding axon growth at these junctures are netrin-1 (onh) and ephrin-B (chiasm). In the optic tectum where RGC axon terminals are arrayed in topographic order, we present experimental evidence to suggest that in the dorso-ventral dimension, the B-type ephrins and Eph receptors are of prime importance, possibly through attractive interactions. This complements the anterior-posterior topographic mapping known to be mediated through A-type ephrin/Eph repulsive interactions. An emerging theme is that guidance molecules such as ephrin-B and netrin-1 have complex patterns of restricted expression in the pathway and play multiple and changing roles in axon guidance.

Retinal function in infants with optic nerve hypoplasia: electroretinograms to large patterns and photopic flash

“…However, the pathfinding processes for ganglion cells in the retina, optic nerve head and optic chiasm and formation of the retinotopic connections in the brainstem is complex. [47][48][49] Deficiency in any one of these processes could lead to failure of accurate functional connections and excessive apoptosis in the ganglion cell layer. The relationships between the quantity and function of ganglion cells and the development of the more distal retinal cells are poorly understood.…”

Rac1 and RhoA Promote Neurite Outgrowth through Formation and Stabilization of Growth Cone Point Contacts

“…Furthermore, when tension was applied to cells uniaxially, protrusion was inhibited along the sides of the cell parallel to the direction of tension (Katsumi et al, 2002) accompanied by a redistribution of active Rac1 to sites perpendicular to the direction of tension, in effect mimicking the polarized cell morphology seen during directed migration. This raises in ECM composition have also been proposed to underlie RGC axon pathfinding (Mann et al, 2004). In addition to Sema3A, other guidance cues have been shown to affect integrindependent adhesion including Ephrin-A1 (Miao et al, 2000), Slit (Stevens and Jacobs, 2002), Semaphorin 7A (Pasterkamp et al, 2003), and Netrin (Yebra et al, 2003).…”

Molecular regulation of visual system development: more than meets the eye

“…During the long distance of axon pathfinding, RGC growth cones are navigated by a succession of different guidance cues expressed in their local environment Rasband et al 2003;Mann et al 2004;Williams et al 2004). The first pathfinding task for RGCs is to exit the eye through the optic nerve.…”

“…As shown in Figure 5, a ring of chondroitin sulphate prevents RGC axons from spreading toward the peripheral retina, thus confining extension toward the central optic disc. In addition, axon guidance molecules, such as L1, netrin-1, and laminin-1, are involved in retinal axon exit at the optic disc leading to optic nerve formation (Mann et al 2004). L1 is a member of immunoglobulin family of cell adhesion molecules, and blockade of L1 function severely disrupts radial growth cone orientation and rate of outgrowth (Brittis et al 1995).…”