Endocytic trafficking factor VPS45 is essential for spatial regulation of lens fiber differentiation in zebrafish.
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 vps45 mutants. VPS45 belongs to the Sec1/Munc18-like protein family and promotes endosome trafficking, which differentially modulates signal transduction. Ectopic lens fiber differentiation in vps45 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.
['Mochizuki|Toshiaki|T|0000-0001-6401-5605', 'Kojima|Yutaka|Y|', 'Nishiwaki|Yuko|Y|0000-0003-2840-2215', 'Harakuni|Tetsuya|T|', 'Masai|Ichiro|I|0000-0002-6626-6595']
D000818:Animals D002454:Cell Differentiation D004705:Endocytosis D004848:Epithelium D005346:Fibroblast Growth Factors D019012:Integrin beta1 D007908:Lens, Crystalline D009154:Mutation D010641:Phenotype D021381:Protein Transport D016212:Transforming Growth Factor beta D033921:Vesicular Transport Proteins D060449:Wnt Signaling Pathway D015027:Zebrafish D029961:Zebrafish Proteins
Endocytic trafficking VPS45 Lens fiber differentiation Zebrafish