Department of Ophthalmology, University of Rochester, NY 14642, USA.
Neuroscience. 2011 Nov 10;195:9-20. doi: 10.1016/j.neuroscience.2011.08.015. Epub 2011 Aug 12.
During retinogenesis, the basic helix-loop-helix proneural gene math5 (atoh7) initiates the generation of the first-born neurons, retinal ganglion cells (RGCs), by activating a network of RGC transcription factors, including Brn-3b (POU4F2). Herein, we show that the expression of DLX1 and DLX2 is significantly down-regulated in math5-null retina but is markedly increased in Brn-3b-null retina. Interestingly, Brn-3b interacts with DLX1 through its homeodomain, and this interaction represses DLX1 activity. Retrovirus-mediated mis-expression of DLX1 or DLX2 dramatically increases the number of amacrine/bipolar cells and concurrently reduces rod photoreceptors. Conversely, combined ectopic expression of Brn-3b with DLX1 or DLX2 promotes the production of RGCs and inhibits amacrine cell differentiation. Thus, DLX1/2 play an essential role in cell fate selection between amacrine and RGCs. Brn-3b suppresses the role of DLX1/2 through physical interaction and biases the competent precursors toward RGC fates.
在视网膜发生过程中，碱性螺旋-环-螺旋 （basic helix-loop-helix，bHLH） 神经前体细胞基因 math5（atoh7）通过激活包括 Brn-3b（POU4F2）在内的一组视网膜神经节细胞 （retinal ganglion cells，RGCs） 转录因子网络，启动第一代神经元 RGCs 的产生。在此，我们发现 math5 缺失的视网膜中 DLX1 和 DLX2 的表达显著下调，但 Brn-3b 缺失的视网膜中表达显著上调。有趣的是，Brn-3b 通过其同源域与 DLX1 相互作用，这种相互作用抑制了 DLX1 的活性。逆转录病毒介导的 DLX1 或 DLX2 异位表达显著增加了双极/无长突细胞的数量，并同时减少了杆状光感受器细胞。相反，Brn-3b 与 DLX1 或 DLX2 的联合异位表达促进了 RGCs 的产生并抑制了无长突细胞的分化。因此，DLX1/2 在无长突细胞和 RGC 之间的细胞命运选择中发挥着重要作用。Brn-3b 通过物理相互作用抑制了 DLX1/2 的作用，并使有潜能的前体细胞向 RGC 命运分化。
