关键词: Endocytic trafficking Lens fiber differentiation VPS45 Zebrafish

Mesh : Animals Cell Differentiation Endocytosis Epithelium / metabolism Fibroblast Growth Factors / metabolism Integrin beta1 / metabolism Lens, Crystalline / cytology metabolism Mutation / genetics Phenotype Protein Transport Transforming Growth Factor beta / metabolism Vesicular Transport Proteins / genetics metabolism Wnt Signaling Pathway Zebrafish / metabolism Zebrafish Proteins / genetics metabolism

来  源:   DOI:10.1242/dev.170282   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
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.
摘要:
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