Developmental Neurobiology Unit, Okinawa Institute of Science and Technology Graduate University, Tancha 1919-1, Onna, Okinawa 098-0945, Japan.
Developmental Neurobiology Unit, Okinawa Institute of Science and Technology Graduate University, Tancha 1919-1, Onna, Okinawa 098-0945, Japan
Development. 2018 Oct 15;145(20):dev170282. doi: 10.1242/dev.170282.
In vertebrate lens, lens epithelial cells cover the anterior half of the lens fiber core. Lens epithelial cells proliferate, move posteriorly and start to differentiate into lens fiber cells at the lens equator. Although FGF signaling promotes this equatorial commencement of lens fiber differentiation, the underlying mechanism is not fully understood. Here, we show that lens epithelial cells abnormally enter lens fiber differentiation without passing through the equator in zebrafish mutants. VPS45 belongs to the Sec1/Munc18-like protein family and promotes endosome trafficking, which differentially modulates signal transduction. Ectopic lens fiber differentiation in mutants does not depend on FGF, but is mediated through activation of TGFβ signaling and inhibition of canonical Wnt signaling. Thus, VPS45 normally suppresses lens fiber differentiation in the anterior region of lens epithelium by modulating TGFβ and canonical Wnt signaling pathways. These data indicate a novel role of endosome trafficking to ensure equator-dependent commencement of lens fiber differentiation.
在脊椎动物晶状体中，晶状体上皮细胞覆盖晶状体纤维核心的前半部分。晶状体上皮细胞增殖，向后移动，并在晶状体赤道处开始分化为晶状体纤维细胞。虽然 FGF 信号促进了晶状体纤维分化的赤道起始，但这一机制尚未完全阐明。在这里，我们发现在斑马鱼突变体中，晶状体上皮细胞异常地进入晶状体纤维分化，而不经过赤道。VPS45 属于 Sec1/Munc18 样蛋白家族，可促进内体运输，从而对信号转导进行差异化调节。突变体中的异位晶状体纤维分化不依赖于 FGF，而是通过 TGFβ 信号的激活和经典 Wnt 信号的抑制来介导。因此，VPS45 通过调节 TGFβ 和经典 Wnt 信号通路，正常抑制晶状体上皮细胞前区的晶状体纤维分化。这些数据表明内体运输在确保晶状体纤维分化依赖赤道起始中的新作用。
