Hayashi Toshinori, Mizuno Nobuhiko, Owaribe Katsushi, Kuroiwa Atsushi, Okamoto Mitsumasa
Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan.
Differentiation. 2002 May;70(2-3):101-8. doi: 10.1046/j.1432-0436.2002.700205.x.
When a lens is removed from the newt eye, a new lens is regenerated from the pigmented epithelial cells of the dorsal iris, whereas the ventral iris never shows such an ability. It is important to clarify the nature of signaling molecules which act directly on the iris cells to accomplish lens regeneration from the iris and also to gain insight into the mechanism of dorso-ventral difference of the regeneration potential. To examine the effects of exogenous factors, we established an in vitro culture of reaggregates made from dissociated pigmented epithelial cells of dorsal or ventral halves of newt iris. Foci of depigmented cells appeared within the cell reaggregates, regardless of their origins, when the cell reaggregates were cultured with FGF2 or FGF4. In contrast, only the depigmented cells in the dorsal iris cell reaggregates underwent extensive proliferation and developed a lens with the synthesis of lens-specific crystallins, recapitulating the normal lens regeneration. On the other hand, neither FGF8, FGF10, EGF, VEGF, nor IGF promoted lens development from iris cell reaggregates. Consistent with the FGF-specific action, FGFR-specific inhibitor SU5402 suppressed the lens development from the cultured cell reaggregates. These results demonstrated that FGF2 or FGF4 is essential for the in vitro lens regeneration from the pigmented cells of the dorsal iris. In addition, these findings indicated that unequal competence in the dorsal and ventral iris to FGF2/4 contributes to the difference in lens forming ability between them.
当从蝾螈眼中取出晶状体时，新的晶状体由背侧虹膜的色素上皮细胞再生而来，而腹侧虹膜则从未表现出这种能力。阐明直接作用于虹膜细胞以实现从虹膜再生晶状体的信号分子的性质，以及深入了解再生潜能的背腹差异机制非常重要。为了研究外源性因素的作用，我们建立了一种体外培养体系，将蝾螈虹膜背侧或腹侧解离的色素上皮细胞重新聚集形成细胞团聚体。当细胞团聚体与FGF2或FGF4一起培养时，无论其来源如何，细胞团聚体内都会出现色素脱失细胞灶。相比之下，只有背侧虹膜细胞团聚体中的色素脱失细胞经历广泛增殖，并通过合成晶状体特异性晶体蛋白发育成晶状体，重现了正常的晶状体再生过程。另一方面，FGF8、FGF10、EGF、VEGF和IGF均未促进虹膜细胞团聚体形成晶状体。与FGF的特异性作用一致，FGFR特异性抑制剂SU5402抑制了培养的细胞团聚体形成晶状体。这些结果表明，FGF2或FGF4对于从背侧虹膜色素细胞进行体外晶状体再生至关重要。此外，这些发现表明，背侧和腹侧虹膜对FGF2/4的反应能力不同，这导致了它们之间晶状体形成能力的差异。
