Xie Yonggang, Li Xiaosu, Zhang Xian, Mei Shaolin, Li Hongyu, Urso Andreacarola, Zhu Sijun
Department of Neuroscience and Physiology, State University of New York Upstate Medical University, Syracuse, United States.
Department of Biology, Syracuse University, Syracuse, United States.
Elife. 2014 Oct 6;3:e03596. doi: 10.7554/eLife.03596.
Intermediate neural progenitor cells (INPs) need to avoid differentiation and cell cycle exit while maintaining restricted developmental potential, but mechanisms preventing differentiation and cell cycle exit of INPs are not well understood. In this study, we report that the Drosophila homolog of mammalian Sp8 transcription factor Buttonhead (Btd) prevents premature differentiation and cell cycle exit of INPs in Drosophila larval type II neuroblast (NB) lineages. We show that the loss of Btd leads to elimination of mature INPs due to premature differentiation of INPs into terminally dividing ganglion mother cells. We provide evidence to demonstrate that Btd prevents the premature differentiation by suppressing the expression of the homeodomain protein Prospero in immature INPs. We further show that Btd functions cooperatively with the Ets transcription factor Pointed P1 to promote the generation of INPs. Thus, our work reveals a critical mechanism that prevents premature differentiation and cell cycle exit of Drosophila INPs.
中间神经祖细胞（INPs）在维持有限的发育潜能的同时，需要避免分化和退出细胞周期，但是阻止INPs分化和退出细胞周期的机制尚未得到充分了解。在本研究中，我们报道哺乳动物Sp8转录因子Buttonhead（Btd）的果蝇同源物可防止果蝇幼虫II型神经母细胞（NB）谱系中的INPs过早分化和退出细胞周期。我们发现，Btd的缺失会导致成熟INPs的消除，因为INPs过早分化为终末分裂的神经节母细胞。我们提供证据证明，Btd通过抑制未成熟INPs中同源结构域蛋白Prospero的表达来防止过早分化。我们进一步表明，Btd与Ets转录因子Pointed P1协同作用以促进INPs的产生。因此，我们的工作揭示了一种关键机制，该机制可防止果蝇INPs过早分化和退出细胞周期。
