Expression of SPIG1 Reveals Development of a Retinal Ganglion Cell Subtype Projecting to the Medial Terminal Nucleus in the Mouse

Abstract

Visual information is transmitted to the brain by roughly a dozen distinct types of retinal ganglion cells (RGCs) defined by a characteristic morphology, physiology, and central projections. However, our understanding about how these parallel pathways develop is still in its infancy, because few molecular markers corresponding to individual RGC types are available. Previously, we reported a secretory protein, SPIG1 (clone name; D/Bsp120I #1), preferentially expressed in the dorsal region in the developing chick retina. Here, we generated knock-in mice to visualize SPIG1-expressing cells with green fluorescent protein. We found that the mouse retina is subdivided into two distinct domains for SPIG1 expression and SPIG1 effectively marks a unique subtype of the retinal ganglion cells during the neonatal period. SPIG1-positive RGCs in the dorsotemporal domain project to the dorsal lateral geniculate nucleus (dLGN), superior colliculus, and accessory optic system (AOS). In contrast, in the remaining region, here named the pan-ventronasal domain, SPIG1-positive cells form a regular mosaic and project exclusively to the medial terminal nucleus (MTN) of the AOS that mediates the optokinetic nystagmus as early as P1. Their dendrites costratify with ON cholinergic amacrine strata in the inner plexiform layer as early as P3. These findings suggest that these SPIG1-positive cells are the ON direction selective ganglion cells (DSGCs). Moreover, the MTN-projecting cells in the pan-ventronasal domain are apparently composed of two distinct but interdependent regular mosaics depending on the presence or absence of SPIG1, indicating that they comprise two functionally distinct subtypes of the ON DSGCs. The formation of the regular mosaic appears to be commenced at the end of the prenatal stage and completed through the peak period of the cell death at P6. SPIG1 will thus serve as a useful molecular marker for future studies on the development and function of ON DSGCs.

Full-length axon regeneration in the adult mouse optic nerve and partial recovery of simple visual behaviors

“…DSGCs that respond to upward and downward motions (23), and was heavily innervated in some of our Group I mice. DSGCs that respond selectively to temporal-to-nasal motion project to other parts of the AOS as well as to the SC and DLG (22).…”

The most numerous ganglion cell type of the mouse retina is a selective feature detector

“…In this region, the W3 cells account for ∼13% of the total RGC population on the basis of previous measurements of total RGC density (25). Other mouse RGC types that have been analyzed to date each amount to <5% of the total population (11)(12)(13)(14)(15)(16)(17)(18).…”

“…In each case, they appear to represent the smallest and densest RGC type. Similarly, the diameter of the W3 dendritic arbor is substantially smaller than those of other genetically marked types (11)(12)(13)(14)(15)(16)(17)(18). Given their dendritic field size, W3-RGCs achieve a coverage factor of ∼4.5 in the region of peak density, such that every point of the image is processed by 4-5 W3 cells on average.…”

“…Unlike other mammals, however, the mouse offers molecular genetic tools that make it possible to mark neurons of specific types, for visualization with fluorescent proteins or manipulation of their cellular functions. Several ganglion cell types have been marked in this way, and this labeling has greatly facilitated their directed study and the discovery of new response properties (11)(12)(13)(14)(15)(16)(17)(18).…”

Morphologically Distinct Classes of Relay Cells Exhibit Regional Preferences in the Dorsal Lateral Geniculate Nucleus of the Mouse

“…For example, in the retina, several classes of retinal ganglion cells (RGCs) have been identified, and many of these seem to comprise separate channels that have distinct molecular, morphological, and functional features, as well as unique patterns of connectivity and central projections (Hattar et al, 2006;Huberman et al, 2008Huberman et al, , 2009Kim et al, 2008Kim et al, , 2010Yonehara et al, 2008;Siegert et al, 2009;Ecker et al, 2010;Hong et al, 2011;Kay et al, 2011;RivlinEtzion et al, 2011). Nonetheless, what remains unexplored in the mouse is whether these separate retinal channels are preserved and recapitulated in a parallel manner onto recipient cells in central target structures.…”