Functional expression of SCL/TAL1 interrupting locus (Stil) protects retinal dopaminergic cells from neurotoxin-induced degeneration

We previously isolated a dominant mutation, night blindness b (nbb), which causes a late-onset of retinal dopaminergic cell degeneration in zebrafish. In this study, we cloned the zebrafish nbb locus. Sequencing results revealed that nbb is a homolog of the vertebrate SCL/TAL1 interrupting locus (Stil). The Stil gene has been shown to play important roles in the regulation of vertebrate embryonic neural development and human cancer cell proliferation. In this study, we demonstrate that functional expression of Stil is also required for neural survival in adult animals. In zebrafish, deficiency in the expression of Stil resulted in increased toxic susceptibility of retinal dopaminergic cells to the neurotoxin 6-hydroxydopamine. Increases in Stil-mediated Shh signaling transduction (i.e., by knocking down the Shh repressor Sufu) prevented dopaminergic cell death induced by neurotoxic insult. The data suggests that the oncogene Stil also plays important roles in neural protection.