Ectopic expression of Msx2 in chick retinal pigmented epithelium cultures suggests a role in patterning the optic vesicle

Abstract

During the initial stages of vertebrate retinogenesis, cells of the optic vesicle adopt one of two alternate cell fates. Cells in the distal-most part of the vesicle, immediately beneath the surface ectoderm, undergo neural differentiation; cells in the proximal part differentiate into retinal pigmented epithelial cells. The mechanisms that establish this pattern of differentiation are poorly understood. In the mouse embryo, Msx2, a homeobox-containing transcription factor, is expressed in cells of the optic vesicle that will form the neural retina, whilst the developing retinal pigmented epithelium (RPE) does not express this gene. Msx2 could therefore be involved in patterning the optic vesicle into neural and pigmented domains. To explore this possibility we ectopically expressed mouse Msx2 in cultures of chick RPE cells. Compared with cultures transfected with a control construct, Msx2-transfected cultures contained fewer cells expressing the RPE marker, Mitf, and more cells expressing class III β-tubulin, a neuronal marker. In addition a small proportion of Msx2-transfected cells acquired a neural-like morphology. These results show that Msx2 can suppress the differentiated state of RPE cells and promote their differentiation into neural cell types. We suggest that Msx2 may pattern the optic vesicle into neural and pigmented domains by affecting the balance between RPE and neural retina differentiation.