Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556; Department of Physiology, Nankai University, Tianjin, China 370001.
Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556.
J Biol Chem. 2014 Mar 7;289(10):6934-6940. doi: 10.1074/jbc.M113.506295. Epub 2014 Jan 27.
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.
人类癌基因 SCL/TAL1 中断基因座(Stil)在脊椎动物物种中高度保守。先前,我们在斑马鱼突变体(夜盲症 b,nbb)中鉴定出 Stil 基因的同源物,该突变体在视网膜中表现出神经缺陷(例如多巴胺能细胞退化和/或缺乏再生)。在这项研究中,我们研究了 Stil 在成年斑马鱼视网膜变性后细胞增殖中的作用。我们证明,Stil 基因表达的敲低或 Sonic hedgehog(Shh)信号转导的抑制会降低细胞增殖率。相反,Shh 信号转导的激活促进细胞增殖。在 nbb(+/-) 视网膜中,抑制 SUFU(Shh 通路中的抑制剂)可挽救因 Stil 基因表达下调而导致的细胞增殖缺陷。后一组数据表明,Stil 通过 Shh 信号转导通路在细胞增殖中发挥作用。