The role of Pax-6 in lens regeneration

Abstract

Pax-6 is a master regulator of eye development and is expressed in the dorsal and ventral iris during newt lens regeneration. We show that expression of Pax-6 during newt lens regeneration coincides with cell proliferation. By knocking down expression of Pax-6 via treatment with morpholinos, we found that proliferation of iris pigment epithelial cells was dramatically reduced both in vitro and in vivo, and, as a result, lens regeneration was significantly retarded. However, induction of dedifferentiation in the dorsal iris was not inhibited. Pax-6 knockdown early in lens regeneration resulted in inhibition of crystallin expression and retardation of lens fiber induction. Once crystallin expression and differentiation of lens fibers has ensued, however, loss of function of Pax-6 did not affect crystallin expression and lens fiber maintenance, even though the effects on proliferation persisted. These results conclusively show that Pax-6 is associated with distinct early events during lens regeneration, namely control of cell proliferation and subsequent lens fiber differentiation.newt ͉ morpholino ͉ proliferation ͉ crystallin

MicroRNAs and regeneration: Let-7 members as potential regulators of dedifferentiation in lens and inner ear hair cell regeneration of the adult newt

“…These miRNAs may become indispensable tools to probe and understand the remarkable regenerative capabilities in salamanders and possibly allow extension in other animals. Since miRNAs are relatively short they can be easily transfected in vivo the same way as morpholinos [27]. As techniques to overexpress or down-regulate miRNAs are becoming more advanced and available we will be able to delineate the function and role of these miRNAs in regeneration.…”

Foxe view of lens development and disease

“…Whereas the lens will readily regenerate in some amphibians (Eguchi, 1967;Eguchi, 1988;Stone, 1953;Stone, 1967;Wolf, 1895), this ability is much more limited in mammals. In newts, the dorsal iris pigment epithelium can be induced to regenerate a lens by lentectomy (Del Rio- Tsonis et al, 1998;Madhavan et al, 2006;Tsonis et al, 2004). This process of lens regeneration seems to be true transdifferentiation, as fully differentiated iris cells dedifferentiate and then redifferentiate into lens cells (Del Rio-Tsonis and Tsonis, 2003).…”

Signaling during lens regeneration

“…Treatment with the morpholino at early stages of lens regeneration resulted in a decrease in crystallin expression and slowing of lens fiber induction. Crystallin synthesis and lens fiber maintenance were not affected upon treatment with the Pax-6 morpholino after these processes had already ensued [46].…”