Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
Dev Cell. 2010 Jan 19;18(1):126-35. doi: 10.1016/j.devcel.2009.12.007.
To ensure normal development and maintenance of homeostasis, the extensive developmental potential of stem cells must be functionally distinguished from the limited developmental potential of transit amplifying cells. Yet the mechanisms that restrict the developmental potential of transit amplifying cells are poorly understood. Here we show that the evolutionarily conserved transcription factor dFezf/Earmuff (Erm) functions cell-autonomously to maintain the restricted developmental potential of the intermediate neural progenitors generated by type II neuroblasts in Drosophila larval brains. Although erm mutant intermediate neural progenitors are correctly specified and show normal apical-basal cortical polarity, they can dedifferentiate back into a neuroblast state, functionally indistinguishable from normal type II neuroblasts. Erm restricts the potential of intermediate neural progenitors by activating Prospero to limit proliferation and by antagonizing Notch signaling to prevent dedifferentiation. We conclude that Erm dependence functionally distinguishes intermediate neural progenitors from neuroblasts in the Drosophila larval brain, balancing neurogenesis with stem cell maintenance.
为了确保正常的发育和内稳态的维持,干细胞的广泛发育潜能必须在功能上与过渡扩增细胞的有限发育潜能区分开来。然而,限制过渡扩增细胞发育潜能的机制还知之甚少。在这里,我们表明,进化上保守的转录因子 dFezf/Earmuff (Erm) 自主发挥作用,维持果蝇幼虫大脑中 II 型神经母细胞产生的中间神经祖细胞的受限发育潜能。尽管 erm 突变体中间神经祖细胞被正确指定并显示出正常的顶底皮质极性,但它们可以返回到神经母细胞状态,在功能上与正常的 II 型神经母细胞无法区分。Erm 通过激活 Prospero 来限制增殖并拮抗 Notch 信号来阻止去分化,从而限制中间神经祖细胞的潜能。我们得出结论,Erm 依赖性在功能上区分了果蝇幼虫大脑中的中间神经祖细胞和神经母细胞,在神经发生和干细胞维持之间取得平衡。