Transcription of the SCL/TAL1 interrupting locus (Stil) is required for cell proliferation in adult zebrafish retinas

The human oncogene SCL/TAL1 interrupting locus (Stil) is highly conserved in vertebrate species. Previously, we identified a homolog of the Stil gene in zebrafish (night blindness b; nbb) which causes neural defects in the retina. In heterozygous nbb+/- retinas, the number of dopaminergic (DA) cells decreases after 4 months of age. In this research, we examined the roles of Stil in cell proliferation in adult zebrafish retinas. We demonstrated that knock-down of Stil gene expression or inhibition of Sonic hedgehog (Shh) signaling transduction decreases the rate of cell proliferation. In contrast, activation of Shh signal transduction promotes cell proliferation. In nbb+/- retinas, inhibition of SUFU (a repressor in the Shh pathway) rescues the defects in cell proliferation due to down-regulation of Stil gene expression. The latter data suggest that Stil plays roles in cell proliferation through the Shh signal transduction pathway.