Onecut 1 and Onecut 2 are potential regulators of mouse retinal development

Abstract

Our current study focuses on the expression of two members of the onecut transcription factor family, One-cut1 (Oc1) and Onecut2 (Oc2), in the developing mouse retina. By immunofluorescence staining, we found that Oc1 and Oc2 had very similar expression patterns throughout retinal development. Both factors started to be expressed in the retina at around embryonic day (E) 11.5. At early stages (E11.5 and E12.5), they were expressed in both the neuroblast layer (NBL) and ganglion cell layer (GCL). As development progressed (from E14.5 to postnatal day [P] 0), expression diminished in the retinal progenitor cells and became more restricted to the GCL. By P5, Oc1 and Oc2 were expressed at very low levels in the GCL. By co-labeling with transcription factors known to be involved in retinal ganglion cell (RGC) development, we found that Oc1 and Oc2 had extensive overlap with Math5 in the NBL, and that they completely overlapped with Pou4f2 and Isl1 in the GCL, but only partially in the NBL. Co-labeling of Oc1 with cell cycle markers confirmed that Oc1 was expressed in both proliferating retinal progenitors and postmitotic retinal cells. In addition, we demonstrated that expression of Oc1 and Oc2 did not require Math5, Isl1, or Pou4f2. Thus, Oc1 and Oc2 may regulate the formation of RGCs in a pathway independent of Math5, Pou4f2, and Isl1. Furthermore, we showed that Oc1 and Oc2 were expressed in both developing and mature horizontal cells (HCs). Therefore the two factors may also function in the genesis and maintenance of HCs. J. Comp. Neurol. 520:952–969, 2012.

Onecut1 and Onecut2 redundantly regulate early retinal cell fates during development

“…This defect likely resulted from abnormal OPL formation, as similar but less-severe phenotypes also were observed in the single-knockout retinas, where the cone numbers did not change ( Fig. S2D) (15). Next, we examined how the two cone subtypes were affected in the DKO retina, using whole-mount immunolabeling of S-and M-cones with anti-S-opsin and anti-M-opsin, respectively (Fig.…”

“…However, at P16 and P25, there was a marked increase in the number of TUNEL + cells in DKO retinas, relative to controls, but these cells were largely confined to the photoreceptor layer ( Fig. S6 M-P and R), which was likely secondary to the loss of HCs, as is the case in the Oc1-null retina (15). Therefore, apoptosis did not contribute to the reduced number of HCs, cones, or RGCs in the DKO retina.…”

“…At E14.5, the mouse retina contains Oc1-expressing RPCs in the outermost ventricular zone, which overlap with early cone makers, suggesting a role for Oc1 in cone genesis (15,17). However, Oc1-null retinas did not show any change in the cone population except for reduction in the numbers of cone pedicles (14), likely a secondary effect from the loss of HCs and the subsequent defective development of the OPL.…”

“…In the mouse, three onecut factors, Onecut1 (Oc1), Onecut2 (Oc2), and Onecut3 (Oc3), with essentially identical DNA-binding domains exist (13). All three of these factors are expressed in the mouse retina, with Oc1 and Oc2 being at high levels (14,15). Oc1 and Oc2 have overlapping expression patterns in RPCs at early developmental stages as well as in precursors of RGCs, cones, and HCs throughout development (15).…”

“…All three of these factors are expressed in the mouse retina, with Oc1 and Oc2 being at high levels (14,15). Oc1 and Oc2 have overlapping expression patterns in RPCs at early developmental stages as well as in precursors of RGCs, cones, and HCs throughout development (15). The temporal and spatial patterns of Oc1 and Oc2 expression indicate that they likely function in the early retinal cell types.…”