Dendritic and axonal targeting patterns of a genetically-specified class of retinal ganglion cells that participate in image-forming circuits

Jason W Triplett,Wei Wei,David A Feldheim,Marla B Feller,Neal T Sweeney,Cristina Gonzalez,Andrew D Huberman

doi:10.1186/1749-8104-9-2

Abstract

BackgroundThere are numerous functional types of retinal ganglion cells (RGCs), each participating in circuits that encode a specific aspect of the visual scene. This functional specificity is derived from distinct RGC morphologies and selective synapse formation with other retinal cell types; yet, how these properties are established during development remains unclear. Islet2 (Isl2) is a LIM-homeodomain transcription factor expressed in the developing retina, including approximately 40% of all RGCs, and has previously been implicated in the subtype specification of spinal motor neurons. Based on this, we hypothesized that Isl2+ RGCs represent a related subset that share a common function.ResultsWe morphologically and molecularly characterized Isl2+ RGCs using a transgenic mouse line that expresses GFP in the cell bodies, dendrites and axons of Isl2+ cells (Isl2-GFP). Isl2-GFP RGCs have distinct morphologies and dendritic stratification patterns within the inner plexiform layer and project to selective visual nuclei. Targeted filling of individual cells reveals that the majority of Isl2-GFP RGCs have dendrites that are monostratified in layer S3 of the IPL, suggesting they are not ON-OFF direction-selective ganglion cells. Molecular analysis shows that most alpha-RGCs, indicated by expression of SMI-32, are also Isl2-GFP RGCs. Isl2-GFP RGCs project to most retino-recipient nuclei during early development, but specifically innervate the dorsal lateral geniculate nucleus and superior colliculus (SC) at eye opening. Finally, we show that the segregation of Isl2+ and Isl2- RGC axons in the SC leads to the segregation of functional RGC types.ConclusionsTaken together, these data suggest that Isl2+ RGCs comprise a distinct class and support a role for Isl2 as an important component of a transcription factor code specifying functional visual circuits. Furthermore, this study describes a novel genetically-labeled mouse line that will be a valuable resource in future investigations of the molecular mechanisms of visual circuit formation.

Highlights

There are numerous functional types of retinal ganglion cells (RGCs), each participating in circuits that encode a specific aspect of the visual scene
Isl2 expression becomes restricted to the ganglion cell layer (GCL), where it is expressed in approximately 40% of all RGCs
Crosssectional analysis showed that in addition to cells in the GCL, green fluorescent protein (GFP) is expressed in cells in the inner nuclear layer (INL), which resemble bipolar cells

Summary

Introduction

There are numerous functional types of retinal ganglion cells (RGCs), each participating in circuits that encode a specific aspect of the visual scene. Isl expression becomes restricted to the ganglion cell layer (GCL), where it is expressed in approximately 40% of all RGCs. Previous studies show that Isl plays a critical role in determining the laterality of RGC projections arising from the ventral-temporal retina [16], but its role in fate specification in the retina remains unclear. Previous studies show that Isl plays a critical role in determining the laterality of RGC projections arising from the ventral-temporal retina [16], but its role in fate specification in the retina remains unclear Based on this expression pattern in the retina and previously described functions, Isl is ideally situated to mediate RGC cell type specification

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