Foxn4 controls the genesis of amacrine and horizontal cells by retinal progenitors
Foxn4 controls the genesis of amacrine and horizontal cells by retinal progenitors
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DOI：
10.1016/j.neuron.2004.08.041
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发表时间：
2004-09-16
期刊：
影响因子：
16.2
通讯作者：
Xiang, MQ
中科院分区：
文献类型：
--
作者：
Li, SG;Mo, ZQ;Xiang, MQ
在脊椎动物视网膜发生过程中，从多能祖细胞中指定了七类细胞。迄今为止，视网膜祖细胞决定多能细胞命运的机制仍然知之甚少。在这里，我们表明，Foxn 4翼螺旋/叉头转录因子在小鼠视网膜发生过程中有丝分裂祖细胞的一个子集中表达。Foxn 4的靶向破坏在很大程度上消除了无长突神经元并完全消除了水平细胞，而Foxn 4的过表达强烈促进了无长突细胞的命运。这些结果表明，Foxn 4是必要的和足够的承诺的无长突细胞的命运，是非冗余所需的水平细胞的发生。此外，我们提供的证据表明，Foxn 4通过激活视网膜生成因子Math 3，NeurOD 1和Prox 1的表达来控制无长突细胞和水平细胞的形成。我们的数据表明，Foxn 4与其他关键的视网膜生成因子合作，介导视网膜祖细胞的多能分化的模型。
During vertebrate retinogenesis, seven classes of cells are specified from multipotent progenitors. To date, the mechanisms underlying multipotent cell fate determination by retinal progenitors remain poorly understood. Here, we show that the Foxn4 winged helix/ forkhead transcription factor is expressed in a subset of mitotic progenitors during mouse retinogenesis. Targeted disruption of Foxn4 largely eliminates amacrine neurons and completely abolishes horizontal cells, while overexpression of Foxn4 strongly promotes an amacrine cell fate. These results indicate that Foxn4 is both necessary and sufficient for commitment to the amacrine cell fate and is nonredundantly required for the genesis of horizontal cells. Furthermore, we provide evidence that Foxn4 controls the formation of amacrine and horizontal cells by activating the expression of the retinogenic factors Math3, NeurOD1, and Prox1. Our data suggest a model in which Foxn4 cooperates with other key retinogenic factors to mediate the multipotent differentiation of retinal progenitors.