The other pigment cell: specification and development of the pigmented epithelium of the vertebrate eye

Abstract

SummaryVertebrate retinal pigment epithelium (RPE) cells are derived from the multipotent optic neuroepithelium, develop in close proximity to the retina, and are indispensible for eye organogenesis and vision. Recent advances in our understanding of RPE development provide evidence for how critical signaling factors operating in dorso-ventral and distal-proximal gradients interact with key transcription factors to specify three distinct domains in the budding optic neuroepithelium: the distal future retina, the proximal future optic stalk/optic nerve, and the dorsal future RPE. Concomitantly with domain specification, the eye primordium progresses from a vesicle to a cup, RPE pigmentation extends towards the ventral side, and the future ciliary body and iris form from the margin zone between RPE and retina. While much has been learned about the molecular networks controlling RPE cell specification, key questions concerning the cell proliferative parameters in RPE and the subsequent morphogenetic events still need to be addressed in greater detail.Key words: Mitf/Otx/Chx10/Pax6/activin/sonic hedgehog/fibroblast growth factor/neuroepithelial domain specification/evolution

RBP-Jκ-dependent Notch signaling enhances retinal pigment epithelial cell proliferation in transgenic mice

“…Nevertheless, Tyrp1::NotchIC/1 RPE cells are able to stop proliferation, to differentiate and to produce pigment. It is thus unlikely that sustained Notch signaling activity induces transdifferentiation toward neuroretinal cells as reported in mice carrying Mitf mutations (Bharti et al, 2006).…”

“…In the adult, the RPE cell monolayer supports photoreceptor cells and equally participates in the maintenance of their function, having critical roles in visual pigment regeneration, scavenging of free radicals and transfer of nutrients. In addition, RPE cells are essential for the critical phagocytosis and continuous renewal of the photoreceptor outer segment membranes (Marmorstein et al, 1998;Adler et al, 1999;Schraermeyer and Heimann, 1999;Chow and Lang, 2001;Bharti et al, 2006). Moreover, development and maintenance of the RPE and the periocular mesenchyme-derived choroid and sclera are interdependent (Fuhrmann et al, 2000;Matt et al, 2005).…”

“…Both pigment cells produce melanin, but have adopted distinct regulatory elements controlling the expression of pigment-cell-specific genes, such as tyrosinase, Tyrp1 and Dct, probably because of an independent evolution of these regulatory networks (Murisier et al, 2006(Murisier et al, , 2007. Moreover, severe mutations of Mitf lead to death of melanocytes, whereas RPE cells survive and hyperproliferate (Bumsted and Barnstable, 2000;Nguyen and Arnheiter, 2000;Bharti et al, 2006).…”

Transcription Factor SOX9 Plays a Key Role in the Regulation of Visual Cycle Gene Expression in the Retinal Pigment Epithelium

“…The role of transcription factors in the RPE has been studied most extensively in development. For example, the crucial role of MITF (11) and OTX2 (12) in RPE development is well documented. The finding that some transcription factors that are critical in RPE development are continuously expressed into mature stages raises the question as to what roles they play in adult RPE.…”

“…Among the key transcription factors required for RPE specification and differentiation are microphthalmia-associated transcription factor (MITF) (11) and orthodenticle homeobox 2 (OTX2) (12). Disruption of either gene or their upstream regulator ␤-catenin in mouse RPE results in transdifferentiation of the RPE into neural retina-like tissues (12)(13)(14).…”