Early B-cell factors are required for specifying multiple retinal cell types and subtypes from postmitotic precursors.
Early B-cell factors are required for specifying multiple retinal cell types and subtypes from postmitotic precursors.
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DOI：
10.1523/jneurosci.2187-10.2010
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发表时间：
2010-09-08
期刊：
影响因子：
--
通讯作者：
Xiang M
中科院分区：
文献类型：
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作者：
Jin K;Jiang H;Mo Z;Xiang M
哺乳动物视网膜中功能性视网膜回路的建立关键取决于六类神经元的正确产生和组装，其中五类神经元由两种或更多种亚型组成，所述亚型在形态、生理特性和/或层下位置上不同。这些不同的神经元类型和亚型如何在视网膜发生过程中出现仍然在很大程度上有待于在分子水平上定义。在这里，我们表明，所有四个家庭成员的EBF螺旋-环-螺旋（HLH）转录因子类似地表达在小鼠视网膜发生在几个神经元类型和亚型，包括神经节，无长突，双极和水平细胞，它们在神经节细胞中的表达依赖于神经节细胞特异性因子Brn 3b。错误表达的EBF偏向视网膜前体细胞朝向非AII甘氨酸能无长突细胞、2型OFF锥双极细胞和水平细胞的命运，而显性负EBF抑制这些细胞以及神经节细胞的分化。通过RNAi减少Ebf 1表达导致与显性负性Ebf类似的抑制作用，有效地中和野生型Ebf 1的促进作用，但对RNAi抗性Ebf 1的促进作用没有影响。这些数据表明，Ebfs对于指定非AII甘氨酸能无长突、2型关闭锥体双极和水平细胞来说是必要且充分的，而它们对于指定神经节细胞来说只是必要的但不是充分的;并进一步表明Ebfs可能协调和合作与其他视网膜原因子，以确保不同视网膜细胞类型和亚型的正确规范和分化。
The establishment of functional retinal circuits in the mammalian retina depends critically on the proper generation and assembly of six classes of neurons, five of which consist of two or more subtypes that differ in morphologies, physiological properties and/or sublaminar positions. How these diverse neuronal types and subtypes arise during retinogenesis still remain largely to be defined at the molecular level. Here we show that all four family members of the Ebf helix-loop-helix (HLH) transcription factors are similarly expressed during mouse retinogenesis in several neuronal types and subtypes including ganglion, amacrine, bipolar and horizontal cells, and that their expression in ganglion cells depends on the ganglion cell specification factor Brn3b. Misexpressed Ebfs bias retinal precursors toward the fates of non-AII glycinergic amacrine, Type 2 OFF-cone bipolar and horizontal cells whereas a dominant-negative Ebf suppresses the differentiation of these cells as well as ganglion cells. Reducing Ebf1 expression by RNAi leads to an inhibitory effect similar to that of the dominant-negative Ebf, effectively neutralizes the promotive effect of wild-type Ebf1 but has no impact on the promotive effect of an RNAi-resistant Ebf1. These data indicate that Ebfs are both necessary and sufficient for specifying non-AII glycinergic amacrine, Type 2 OFF-cone bipolar and horizontal cells, whereas they are only necessary but not sufficient for specifying ganglion cells; and further suggest that Ebfs may coordinate and cooperate with other retinogenic factors to ensure proper specification and differentiation of diverse retinal cell types and subtypes.