Differential Role of Slits in Dorsal versus Ventral Retinal Axon Guidance: Figure 1.

Abstract

Editor's Note: These short reviews of a recent paper in the Journal, written exclusively by graduate students or postdoctoral fellows, are intended to mimic the journal clubs that exist in your own departments or institutions. For more information on the format and purpose of the Journal Club, please see http://www.jneurosci.org/misc/ifa_features.shtml. The establishment of accurate projections is essential to the precise functioning of neuronal structures. Furthermore, the acquisition of appropriate wiring patterns by neurons in sensory systems ensures the viability of the entire organism. Partly for this reason, the retina has, for over a century, grabbed the attention of well known scientists. Santiago Ramó n y Cajal's (1911) pioneering work provided precise anatomical descriptions of the architecture of the retina, leading him to propose hypotheses about its function. In 1963, Roger Wolcott Sperry performed his eyeball rotation experiment, still taught to almost every student of neuroscience and developmental biology, which showed that growing axons are guided by chemical factors in their environment. Sperry's (1963) chemoaffinity hypothesis spurred a series of studies to investigate the role of axon guidance molecules in the development of the visual system, including the one that is the focus of a recent article in the Journal of Neuroscience by Thompson et al. (2006a). The authors addressed the role of Slit proteins in intraretinal axon guidance, the mechanisms by which axons growing from retinal ganglion cells (RGCs) form a layer at the internal surface of the retina, converging toward the optic disc. These projections then exit the retina to form the optic nerve. The pathfinding process of RGC axons is essential to the development of the visual system as defects in the internal organization of the retina affect the proper functioning of the eye. The authors focused on Slit1 and Slit2, two secreted proteins whose role as chemorepellents and growth inhibitors is well documented in different axonguidance systems. In particular, they took advantage of the availability of slit1-and slit2-deficient mice (Plump et al., 2002) to analyze the effects of the loss of these molecules on the establishment of retinal architecture. Differential Role of Slits in Dorsal versus Ventral Retinal Axon GuidanceMutant mice were designed to express tau-green fluorescent protein (GFP) under the control of the endogenous slit1 or slit2 promoters, so that any cell that would normally express slit mRNA would express GFP in cell bodies and processes. Previous studies using in situ hybridization, a technique that allows identification of Slit expression in cell bodies but not fibers (the vast majority of mRNAs being restricted to the soma), demonstrated that both genes are expressed in the RGC layer of the retina (Erskine et al., 2000), but the identity of the expressing cells was not clear. The observation that GFP immunoreactivity is evident all along the RGC axon paths [Thompson et al. (2006a) performed GFP-staining on longitudi...