The transcription factors Prdm1 (Blimp1) and Vsx2 (Chx10) work downstream of Otx2 to regulate photoreceptor and bipolar cell fates in the developing retina. Mice that lack Vsx2 fail to form bipolar cells while Prdm1 mutants form excess bipolars at the direct expense of photoreceptors. Excess bipolars in Prdm1 mutants appear to derive from rods, suggesting that photoreceptor fate remains mutable for some time after cells become specified. Here we tested whether bipolar cell fate is also plastic during development. To do this, we created a system to conditionally misexpress Prdm1 at different stages of bipolar cell development. We found that Prdm1 blocks bipolar cell formation if expressed before the fate choice decision occurred. When we misexpressed Prdm1 just after the decision to become a bipolar cell was made, some cells were reprogrammed into photoreceptors. In contrast, Prdm1 misexpression in mature bipolar cells did not affect cell fate. We also provide evidence that sustained misexpression of Prdm1 was selectively toxic to photoreceptors. Our data show that bipolar fate is malleable, but only for a short temporal window following fate specification. Prdm1 and Vsx2 act by stabilizing photoreceptor and bipolar fates in developing OTX2+ cells of the retina.

转录因子Prdm1 ( Blimp1)和Vsx2 (Chx10)在Otx2 的下游起作用，以调节发育中的视网膜中的感光细胞和双极细胞的命运。缺乏Vsx2 的小鼠无法形成双极细胞，而Prdm1突变体以光感受器的直接为代价形成过多的双极细胞。Prdm1突变体中过多的双极细胞似乎来自视杆细胞，这表明在细胞被指定后一段时间内，光感受器的命运仍然是可变的。在这里，我们测试了双极细胞命运在发育过程中是否也是可塑性的。为此，我们创建了一个系统来有条件地错误表达Prdm1在双极细胞发育的不同阶段。我们发现，如果在命运选择决定发生之前表达，Prdm1 会阻止双极细胞的形成。当我们在决定成为双极细胞后错误表达Prdm1 时，一些细胞被重新编程为光感受器。相比之下，成熟双极细胞中的Prdm1错误表达不影响细胞命运。我们还提供证据表明，Prdm1 的持续错误表达对光感受器具有选择性毒性。我们的数据显示双极命运是可塑的，但仅适用于命运规范后的短暂时间窗口。Prdm1和Vsx2 通过稳定视网膜 OTX2+ 细胞中的光感受器和双极命运来发挥作用。