Implication of OTX2 in Pigment Epithelium Determination and Neural Retina Differentiation

Abstract

The expression pattern of Otx2, a homeobox-containing gene, was analyzed from the beginning of eye morphogenesis until neural retina differentiation in chick embryos. Early on, Otx2 expression was diffuse throughout the optic vesicles but became restricted to their dorsal part when the vesicles contacted the surface ectoderm. As the optic cup forms, Otx2 was expressed only in the outer layer, which gives rise to the pigment epithelium. This early Otx2 expression pattern was complementary to that of PAX2, which localizes to the ventral half of the developing eye and optic stalk. Otx2 expression was always observed in the pigment epithelium at all stages analyzed but was extended to scattered cells located in the central portion of the neural retina around stage 22. The number of cells expressing Otx2 transcripts increased with time, following a central to peripheral gradient. Bromodeoxyuridine labeling in combination with immunohistochemistry with anti-OTX2 antiserum and different cell-specific markers were used to determine that OTX2-positive cells are postmitotic neuroblasts undergoing differentiation into several, if not all, of the distinct cell types present in the chick retina. These data indicate that Otx2 might have a double role in eye development. First, it might be necessary for the early specification and subsequent functioning of the pigment epithelium. Later, OTX2 expression might be involved in retina neurogenesis, defining a differentiation feature common to the distinct retinal cell classes.

XOtx5b and XOtx2regulate photoreceptor and bipolar fates in theXenopusretina

“…Our results confirm other studies done on chick (Bovolenta et al, 1997) that early in retina formation, XOtx2 transcripts are found in all layers of the neural retina. Yet, if XOtx2 is involved in bipolar cell specification in Xenopus, why do not all cells become bipolar cells?…”

“…otd (also known as oc; ocelliless) is the only otd/Otx family member identified in Drosophila and it contributes to head formation (Finkelstein et al, 1990). The vertebrate homologues of otd include Otx1, Otx2,Otx3,Otx4,Otx5,Otx5b (96% similar to Otx5) and Crx, which are all involved in anterior embryo and sensory organ formation (Acampora et al, 1998a;Acampora et al, 1998b;Acampora et al, 1996;Acampora and Simeone, 1999;Andreazzoli et al, 1997;Bovolenta et al, 1997;Furukawa et al, 1997;Gammill and Sive, 1997;Kablar et al, 1996;Kuroda et al, 2000;MartinezMorales et al, 2001;Pannese et al, 1995;Sauka-Spengler et al, 2001;Suda et al, 1999;Vignali et al, 2000). The first vertebrate homologues of otd, Otx1 and Otx2, were characterised in mouse (Simeone et al, 1992).…”

“…Some otd/Otx family members are expressed in both photoreceptors and bipolar cells while others are expressed in one cell type or the other. Zebrafish Crx (Liu et al, 2001), mouse Otx2 (Baas et al, 2000;Bovolenta et al, 1997) and Xenopus Otx5b (see below), for example, are expressed by both bipolars and photoreceptors, while mouse Crx is expressed only in photoreceptors cells (Chen et al, 1997;Furukawa et al, 1997) and Xenopus Otx2 is found in bipolar cells but not photoreceptors (Kablar et al, 1996;Perron et al, 1998). We were therefore interested to know what roles XOtx5b and XOtx2 play in retinal development, and specifically whether they contribute to the switch between these two cell fates.…”

Meis1 coordinates a network of genes implicated in eye development and microphthalmia

“…Furthermore, the number of Otx2 + retinal progenitors (supplementary material Fig. S1G,I) (Bovolenta et al, 1997) and that of Tuj1 + or islet 1/2 (Isl1/2) + differentiating neurons (Esteve et al, 2011) was reduced in E12/E13 Meis1 −/− retinas (Fig. 2J,L,M,O).…”

Chromosomal Rearrangements and Novel Genes in Disorders of Eye Development, Cataract and Glaucoma

“…OTX2 is a bicoid-type homeodomain transcription factor important in retinal differentiation and fore and midbrain development (Bovolenta et al, 1997;Simeone et al, 1993). Heterozygous loss of function mutations in OTX2 are a rare cause of the anophthlamia or severe microphthalmia phenotype occurring in approximately 2% of patients (Table 1).…”