Transcription of the SCL/TAL1 Interrupting Locus (Stil) Is Required for Cell Proliferation in Adult Zebrafish Retinas

Lei Sun,Ping Li,Aprell L Carr,Ryne Gorsuch,Clare Yarka,Jingling Li,Michael Bartlett,Delaney Pfister,David R Hyde,Lei Li

doi:10.1074/jbc.m113.506295

Lei Sun, Ping Li + Show 8 more

Open Access

https://doi.org/10.1074/jbc.m113.506295

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Abstract

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 mutant (night blindness b, nbb), which showed neural defects in the retina (e.g. dopaminergic cell degeneration and/or lack of regeneration). In this research, we examined the roles of Stil in cell proliferation after degeneration in adult zebrafish retinas. We demonstrated that knockdown 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 play a role in cell proliferation through the Shh signal transduction pathway.

Highlights

SCL/TAL1 interrupting locus (Stil) is a human oncogene that is involved in cancer cell proliferation and survival
We examined the role of Stil gene expression in cell proliferation in adult zebrafish retinas
Cell Proliferation—To demonstrate the involvement of Sonic hedgehog (Shh) signaling in DA cell proliferation, we examined cell proliferation responses in wild-type fish treated with cyclopamine and

Summary

Background

Results: In adult zebrafish retinas, knockdown of Stil expression decreases the rate of cell proliferation after degeneration. We demonstrated that knockdown of Stil gene expression or inhibition of Sonic hedgehog (Shh) signaling transduction decreases the rate of 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 play a role in cell proliferation through the Shh signal transduction pathway. We examined the role of Stil gene expression in cell proliferation in adult zebrafish retinas. Stil Is Required for Cell Proliferation involvement of Stil and Stil-mediated Shh signal transduction in cell proliferation in adult neural tissues

EXPERIMENTAL PROCEDURES

RESULTS

Inhibition of Shh Signal Transduction Reduced the Rate of