Canonical Wnt signaling is one of intracellular signaling pathways that play crucial roles in vertebrate embryonic development, cell fate determination and maintenance of adult tissue functions. Activation of this pathway is closely associated with cytoplasmic degradation and nuclear accumulation of beta-catenin. Once transported into the nucleus, beta-catenin forms a complex with transcription factor LEF/TCF to drive the transcription of target genes. Currently, many proteins within the membrane, the cytoplasm and the nucleus are known to affect the intracellular localization of beta-catenin and thus control the activity of canonical Wnt signaling.
Nucleoporin p62 (Nup62)localizes in the central channel of nuclear pore complexes (NPCs) and regulates nuclear pore permeability and nucleocytoplasmic transport. 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 the Wnt/beta-catenin pathway positively modulates nup62l transcription, while Bmp signaling acts downstream of Wnt/beta-catenin signaling to negatively regulate nup62l expression. Overexpression of nup62l dorsalized embryos and enhanced gastrula convergence and extension (CE) movements. In contrast, knockdown of Nup62l led to ventralized embryos, an impediment to CE movements, and defects in specification of midline organ progenitors. Mechanistically, Nup62l acts as an activator of Wnt/beta-catenin signaling through interaction with and facilitation of nuclear import of beta-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 beta-catenins in zebrafish.
Obviously, in-depth studies of mechanisms underlying the regulation of Wnt/beta-catenin signaling activity would reveal the asymmetric and tissue-specific activation of canonical Wnt signaling during early development in zebrafish and the activity of intracellular beta-catenin in pathological contexts.