Two Pairs of ON and OFF Retinal Ganglion Cells Are Defined by Intersectional Patterns of Transcription Factor Expression

Abstract

Summary Visual information is conveyed to the brain by axons of >30 retinal ganglion cell (RGC) types. Characterization of these types is a prerequisite to visual perception understanding. Here we identify a family of RGCs that we call F-RGCs based on expression of the transcription factor Foxp2. Intersectional expression of Foxp1 and Brn3 transcription factors divides F-RGCs into four types, comprising two pairs, each composed of closely related cells. One pair, F-miniON and F-miniOFF, shows robust direction selectivity. They are among the smallest RGCs in the mouse retina. The other pair, F-midiON and F-midiOFF, are larger and not direction-selective. Together, F-RGCs comprise >20% of RGCs in the mouse retina, halving the number that remain to be classified and doubling the number of known direction-selective cells. Co-expression of Foxp and Brn3 genes also marks subsets of RGCs in macaques that could be primate homologues of F-RGCs.

Diverse Central Projection Patterns of Retinal Ganglion Cells

“…Cre-expressing) RGCs in two ways. First, we stained sections with antibodies to a panel of cell type-specific markers: (1) RBPMS, which labels RGCs but not amacrine cells (Rodriguez et al, 2014); (2) osteopontin (OPN), which labels alpha RGCs (Duan et al, 2015); (3) CART, which labels ON-OFF direction-selective RGCs (ooDSGCs, Kay et al, 2011); (4) Foxp2, which labels 2 types of small direction-selective RGCs and 2 types of medium-sized direction-nonselective RGCs (Rousso et al, 2016); and (5) parvalbumin (Pvalb), which labels 11 types of RGCs that include alpha RGCs and ooDSGCs, as well as others (Yi et al, 2012; Farrow et al, 2013). In some cases, we also stained sections with antibodies to melanopsin (Opn4), which labels 3 types of intrinsically photosensitive (ip)RGCs (Schmidt et al, 2011) and Brn3a, which labels the majority of RGCs (Badea et al, 2009).…”

“…Lines in which ooDSGCs were selectively labeled (Cdh6-CreER, Cart-Tg1-Cre, and Gpr26-Cre_KO250) fell into this group. This group also included 3 lines in which OFF-DSGCs are labeled (Jam2-CreER, Cdh4-CreER and Foxp2-Cre) (Kim et al, 2008; Rousso et al, 2016). Lines with terminals in all layers of LGd also projected to all layers of SCs.…”

“…In fact, despite intensive effort, few lines have been found in which a reporter is specifically expressed in a single RGC type (Huberman et al, 2008; Kim et al, 2008; Huberman et al, 2009; Trenholm et al, 2011). In other cases, the reporter marks a small number of types, which are often related to each other (Siegert et al, 2009; Kim et al, 2010; Kay et al, 2011; Dhande et al, 2013; Farrow et al, 2013; Duan et al, 2015; Rousso et al, 2016). Indeed, within the retina, and even within just RGCs, single genes are seldom reliable markers of a single cell type (reviewed in Sanes and Masland, 2015).…”

Parallel Computations in Insect and Mammalian Visual Motion Processing

“…The ON–OFF direction-selective retinal ganglion cell, mentioned above (Figure 1C), integrates inputs from both ON and OFF starburst amacrine cells [109]. Other types exist that are either ON or OFF selective [132,140,141]. In the case of recombined signals in fly and mouse, one might ask whether there was a functional purpose to computing the signals separately before the recombination, rather than employing a direction-selective mechanism without ON and OFF pathways, like many models of direction-selectivity [2,3].…”

Ipsilateral and Contralateral Retinal Ganglion Cells Express Distinct Genes during Decussation at the Optic Chiasm

“…The vertebrate retina, with its three cellular layers and six neuronal classes, has been a useful model for studying general principles of neurogenesis and axon guidance. Each class of retinal cells can be further divided into morphologically and functionally distinct subtypes, and recent efforts have identified the molecular programs that establish these differences within neuronal classes, such as amacrine, bipolar, and retinal ganglion cell (RGC) subtypes (Kim et al, 2008; Badea et al, 2009; Kay et al, 2011a, 2011b; Watson et al, 2012; Jiang et al, 2013; Sajgo et al, 2014; Macosko et al, 2015; Osterhout et al, 2015; Sanes and Masland, 2015; Tang et al, 2015; Jin et al, 2015; Rousso et al, 2016; Shekhar et al, 2016). RGCs, as the only projection neurons of the retina, can be additionally distinguished by the laterality of their axonal projection to targets in the thalamus and midbrain.…”