Robo2 is required for Slit-mediated intraretinal axon guidance.

Hannah Thompson,William Andrews,Lynda Erskine,John G Parnavelas

doi:10.1016/j.ydbio.2009.09.034

Hannah Thompson, William Andrews + Show 2 more

Open Access

https://doi.org/10.1016/j.ydbio.2009.09.034

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Abstract

The developing optic pathway has proven one of the most informative model systems for studying mechanisms of axon guidance. The first step in this process is the directed extension of retinal ganglion cell (RGC) axons within the optic fibre layer (OFL) of the retina towards their exit point from the eye, the optic disc. Previously, we have shown that the inhibitory guidance molecules, Slit1 and Slit2, regulate two distinct aspects of intraretinal axon guidance in a region-specific manner. Using knockout mice, we have found that both of these guidance activities are mediated via Robo2. Of the four vertebrate Robos, only Robo1 and Robo2 are expressed by RGCs. In mice lacking robo1 intraretinal axon guidance occurs normally. However, in mice lacking robo2 RGC axons make qualitatively and quantitatively identical intraretinal pathfinding errors to those reported previously in Slit mutants. This demonstrates clearly that, as in other regions of the optic pathway, Robo2 is the major receptor required for intraretinal axon guidance. Furthermore, the results suggest strongly that redundancy with other guidance signals rather than different receptor utilisation is the most likely explanation for the regional specificity of Slit function during intraretinal axon pathfinding.

Highlights

The first step in the formation of functional visual connections is the guidance of retinal ganglion cell (RGC) axons towards the optic disc, their exit point from the eye
Robo2 and, to a lesser extent, Robo1 have been shown previously to be key regulators of RGC axon guidance at the optic chiasm and optic tract (Plachez et al, 2008). We expand these findings and demonstrate clearly that Robo2 is required for the first step in RGC axon guidance, the directed growth of the axons within the retina to exit the eye
Together with previous work (Fricke et al, 2001; Hutson and Chien, 2002; Plachez et al, 2008), these findings provide direct evidence that Robo2 is the predominant Robo required for RGC axon pathfinding and, like its Slit ligands, is essential for RGC axon guidance throughout the entire optic pathway (Plump et al, 2002; Thompson et al, 2006a,b; Plachez et al, 2008)

Summary

Introduction

The first step in the formation of functional visual connections is the guidance of retinal ganglion cell (RGC) axons towards the optic disc, their exit point from the eye. Since vertebrates have multiple Robos, at least two of which are expressed in the developing retina (Erskine et al, 2000; Niclou et al, 2000; Ringstedt et al, 2000; Plachez et al, 2008), could distinct receptors mediate these different aspects of intraretinal axon guidance? The results demonstrate clearly that Robo regulates both aspects of Slit-mediated intraretinal axon pathfinding This suggests strongly that redundant interactions with other guidance signals, rather than different receptor utilisation, underlie the distinct requirements of Slits in dorsal and ventral retina

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