The role of Pax-6 in lens regeneration
The role of Pax-6 in lens regeneration
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DOI：
10.1073/pnas.0601949103
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发表时间：
2006-10-03
影响因子：
11.1
通讯作者：
Del Rio-Tsonis, Katia
中科院分区：
文献类型：
--
作者：
Madhavan, Mayur;Haynes, Tracy L.;Del Rio-Tsonis, Katia
Pax-6是眼睛发育的主要调节因子，在蝾螈透镜再生过程中在背侧和腹侧虹膜中表达。我们发现，在蝾螈透镜再生过程中的Pax-6的表达与细胞增殖相一致。通过用吗啉代处理敲低Pax-6的表达，我们发现虹膜色素上皮细胞的增殖在体外和体内都显著降低，并且，作为结果，透镜再生显著延迟。然而，诱导去分化的背侧虹膜没有受到抑制。在透镜再生早期Pax-6敲低导致晶状体蛋白表达的抑制和透镜纤维诱导的延迟。然而，一旦晶体蛋白表达和透镜纤维分化发生，Pax-6功能丧失并不影响晶体蛋白表达和透镜纤维维持，即使对增殖的影响持续存在。这些结果最终表明，Pax-6与透镜再生过程中的不同早期事件相关，即控制细胞增殖和随后的透镜纤维分化。
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.