Nucleoporin 62-like protein activates canonical Wnt signaling through facilitating the nuclear import of β-catenin in zebrafish

Nucleoporin p62 (Nup62) localizes in the central channel of nuclear pore complexes (NPCs) and regulates nuclear pore permeability and nucleocytoplasmic transport. However, developmental roles of Nup62 in vertebrates remain largely unclear. Zebrafish Nup62-like protein (Nup62l) is a homolog of mammalian Nup62. The nup62l gene is maternally expressed, but its transcripts are ubiquitously distributed during early embryogenesis and enriched in the head, pharynx and intestine of developing embryos. Activation of Wnt/β-catenin pathway positively modulates the nup62l transcription, while Bmp signaling acts downstream of Wnt/β-catenin signaling to negatively regulate the nup62l expression. Overexpression of nup62l dorsalized embryos and enhanced gastrula convergence and extension (CE) movements. Contrarily, knockdown of Nup62l leads to ventralized embryos, an impediment to CE movements and defects in specification of midline organ progenitors. Mechanistically, Nup62l acts as an activator of Wnt/β-catenin signaling through interaction with and facilitating nuclear import of β-catenin-1/2 in zebrafish. Thus, Nup62l regulates dorsoventral patterning, gastrula CE movements and proper specification of midline organ precursors through mediating the nuclear import of β-catenins in zebrafish.