Elliott Jimmy, Jolicoeur Christine, Ramamurthy Vasanth, Cayouette Michel
Institut de recherches cliniques de Montréal (IRCM), Cellular Neurobiology Research Unit, Montréal, QC H2W 1R7, Canada.
Neuron. 2008 Oct 9;60(1):26-39. doi: 10.1016/j.neuron.2008.08.008.
In the developing mouse retina, multipotent retinal progenitor cells (RPCs) give rise to specific retinal cell types at different times, but the molecular mechanisms regulating how RPCs change over time remain unclear. In the Drosophila neuroblast lineage, the zinc finger transcription factor Hunchback (Hb) is both necessary and sufficient to specify early-born neuronal identity. We show here that Ikaros, a mouse ortholog of Hb, is expressed in all early embryonic RPCs, which then give rise to Ikaros-negative RPCs at later stages in the lineage. Remarkably, misexpression of Ikaros in late RPCs is sufficient to confer competence to generate early-born neurons. Conversely, Ikaros mutant mice have reduced numbers of early-born cell types, whereas late-born cell types are not affected. These results suggest a model in which Ikaros expression is both necessary and sufficient to confer early temporal competence to RPCs and raise the possibility that a similar strategy might be used to control the sequential order of cell birth in other parts of the nervous system.
在发育中的小鼠视网膜中,多能视网膜祖细胞(RPCs)在不同时间产生特定的视网膜细胞类型,但调节RPCs随时间变化的分子机制仍不清楚。在果蝇神经母细胞谱系中,锌指转录因子驼背(Hb)对于确定早期生成的神经元身份既是必需的也是充分的。我们在此表明,Hb的小鼠同源物Ikaros在所有早期胚胎RPCs中表达,这些RPCs随后在谱系的后期产生Ikaros阴性的RPCs。值得注意的是,Ikaros在晚期RPCs中的错误表达足以赋予产生早期生成神经元的能力。相反,Ikaros突变小鼠中早期生成的细胞类型数量减少,而晚期生成的细胞类型不受影响。这些结果提示了一种模型,其中Ikaros的表达对于赋予RPCs早期时间能力既是必需的也是充分的,并增加了在神经系统其他部分可能使用类似策略来控制细胞出生顺序的可能性。