Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, OR 97403, USA.
Dev Cell. 2012 Oct 16;23(4):849-57. doi: 10.1016/j.devcel.2012.09.007.
Snail family transcription factors are best known for regulating epithelial-mesenchymal transition (EMT). The Drosophila Snail family member Worniu is specifically transcribed in neural progenitors (neuroblasts) throughout their lifespan, and worniu mutants show defects in neuroblast delamination (a form of EMT). However, the role of Worniu in neuroblasts beyond their formation is unknown. We performed RNA-seq on worniu mutant larval neuroblasts and observed reduced cell-cycle transcripts and increased neural differentiation transcripts. Consistent with these genomic data, worniu mutant neuroblasts showed a striking delay in prophase/metaphase transition by live imaging and increased levels of the conserved neuronal differentiation splicing factor Elav. Reducing Elav levels significantly suppressed the worniu mutant phenotype. We conclude that Worniu is continuously required in neuroblasts to maintain self-renewal by promoting cell-cycle progression and inhibiting premature differentiation.
蜗牛家族转录因子以调控上皮-间充质转化 (EMT) 而闻名。果蝇蜗牛家族成员 Worniu 专门在其整个生命周期的神经祖细胞（神经母细胞）中转录，而 worniu 突变体显示出神经母细胞分层（一种 EMT 形式）缺陷。然而，Worniu 在神经母细胞形成后的作用尚不清楚。我们对 worniu 突变体幼虫神经母细胞进行了 RNA-seq 分析，观察到细胞周期转录本减少，神经分化转录本增加。与这些基因组数据一致，活体成像显示 worniu 突变体神经母细胞在前期/中期转变中出现明显延迟，并增加了保守的神经元分化剪接因子 Elav 的水平。降低 Elav 水平显著抑制了 worniu 突变体的表型。我们得出结论，Worniu 通过促进细胞周期进程和抑制过早分化，在神经母细胞中持续需要以维持自我更新。
