Expression of the LIM‐homeodomain protein Isl1 in the developing and mature mouse retina

Abstract

The mammalian retina is comprised of six major neuronal cell types and is subdivided into more morphological and physiological subtypes. The transcriptional machinery underlying these subtype fate choices is largely unknown. The LIM-homeodomain protein, Isl1, plays an essential role in central nervous system (CNS) differentiation but its relationship to retinal neurogenesis remains unknown. We report here its dynamic spatiotemporal expression in the mouse retina. Among bipolar interneurons, Isl1 expression commences at postnatal day (P)5 and is later restricted to ON-bipolar cells. The intensity of Isl1 expression is found to segregate the pool of ON-bipolar cells into rod and ON-cone bipolar cells with higher expression in rod bipolar cells. As bipolar cell development proceeds from P5-10 the colocalization of Isl1 and the pan-bipolar cell marker Chx10 reveals the organization of ON-center bipolar cell nuclei to the upper portion of the inner nuclear layer. Further, whereas Isl1 is predominantly a ganglion cell marker prior to embryonic day (E)15.5, at E15.5 and later its expression in nonganglion cells expands. We demonstrate that these Isl1-positive, nonganglion cells acquire the expression of amacrine cell markers embryonically, likely representing nascent cholinergic amacrine cells. Taken together, Isl1 is expressed during the maturation of and is later maintained in retinal ganglion cells and subtypes of amacrine and bipolar cells where it may function in the maintenance of these cells into adulthood.

Histone demethylase Jmjd3 is required for the development of subsets of retinal bipolar cells

“…2D). Isl1 is a marker of rod and cone-ON-BP and cholinergic amacrine cells (21,22). The number of Isl1-positive ON-BP cells decreased by about 20% in shJmjd3-transfected retina (Fig.…”

“…To obtain retinal cells enriched for BP cells, we used Isl1, which is a marker of rod-and cone-ON-BP and cholinergic amacrine cells (21,22). We stained permeabilized retinal cells at P9 with an anti-Isl1 antibody, followed by staining with a secondary antibody conjugated with phycoerythrin.…”

“…However, this was difficult to confirm, given the lack of a specific marker for this BP subset. Furthermore, although Isl1 is strictly expressed in the ON-BP subset in the mature retina (21,22,26), Isl1-KO mice also have OFF-BP subset defects, suggesting that Isl1 is transiently expressed in OFF-BP cell precursors (27) and that the precursors of Recoverin-positive cells are found in the Isl1-positive fractions. The level of H3K27me3 at the Cdkn2a (Ink4a) locus was not significantly different between the Isl1-positive and Isl1-negative populations, and that at the Elavl3 locus was slightly higher in Isl1-positive cells.…”

Development and diversification of retinal amacrine interneurons at single cell resolution

“…S4). Two transcription factors, Isl1 and Sox2, that have been implicated in development of cholinergic amacrine cells (16,17) were expressed in all of the profiled cholinergic amacrine cells (Fig. 4).…”

ISL1 and BRN3B co-regulate the differentiation of murine retinal ganglion cells

“…Whereas BRN3B was expressed uniformly in both migrating RGCs in the neuroblast layer (NBL) and the post-migrated RGCs in the ganglion cell layer (GCL), ISL1 expression level appeared to be higher in the GCL and lower in the NBL. The expression of ISL1 was sustained in RGCs in adult mice and was also found in cholinergic amacrine and ON-bipolar cells (Elshatory et al, 2007a;Elshatory et al, 2007b;Galli-Resta et al, 1997). Anti-ISL1 is raised against the C-terminal of ISL1 homeodomain and reacts to ISL1 specifically but also recognizes ISL2 with a lower affinity (Tanabe et al, 1998).…”