All Brn3 genes can promote retinal ganglion cell differentiation in the chick.
All Brn3 genes can promote retinal ganglion cell differentiation in the chick.
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DOI：
10.1242/dev.127.15.3237
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发表时间：
2000-08
期刊：
影响因子：
4.6
通讯作者：
Wei Liu;Suvarna L. Khare;Xuelian Liang;Maureen A. Peters;Xiaoying Liu;C. Cepko;M. Xiang
中科院分区：
文献类型：
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作者：
Wei Liu;Suvarna L. Khare;Xuelian Liang;Maureen A. Peters;Xiaoying Liu;C. Cepko;M. Xiang
在小鼠中的靶向基因破坏研究已经证明了Brn3 POU结构域转录因子基因Brn3a、Brn3b、Brn3c（现在分别称为Pou4f1、Pou4f2、Pou4f3）在感觉神经发育和存活中的关键作用。在小鼠视网膜发生过程中，Brn3b基因在大量的有丝分裂后神经节细胞前体中表达，并且是其早期和终末分化所必需的。与此相反，Brn3a和Brn3c基因，这是后来在神经节细胞中表达，似乎是神经节细胞的发展。为了了解Brn3基因在视网膜发育中功能差异的机制，我们在鸡胚中采用了功能获得的方法。我们发现Brn3b（l）和Brn3b（s），由Brn3b基因编码的两种同种型，以及Brn3a和Brn3c都具有相似的DNA结合和反式激活活性。我们进一步发现，POU域是这些活动所需的最低限度。因此，我们表明，所有这些Brn3蛋白具有类似的能力，以促进神经节细胞的发展时，异位表达在视网膜祖细胞。在鸡视网膜发生过程中，cBrn3c而不是cBrn3b表现出神经节细胞发生的时空表达模式，其错误表达也可以增加神经节细胞的产量。基于这些数据，我们提出，所有的Brn3因子都能够促进视网膜神经节细胞的发育，并且这种潜力可能受到体内表达顺序的限制。
Targeted gene disruption studies in the mouse have demonstrated crucial roles for the Brn3 POU domain transcription factor genes, Brn3a, Brn3b, Brn3c (now called Pou4f1, Pou4f2, Pou4f3, respectively) in sensorineural development and survival. During mouse retinogenesis, the Brn3b gene is expressed in a large set of postmitotic ganglion cell precursors and is required for their early and terminal differentiation. In contrast, the Brn3a and Brn3c genes, which are expressed later in ganglion cells, appear to be dispensable for ganglion cell development. To understand the mechanism that causes the functional differences of Brn3 genes in retinal development, we employed a gain-of-function approach in the chick embryo. We find that Brn3b(l) and Brn3b(s), the two isoforms encoded by the Brn3b gene, as well as Brn3a and Brn3c all have similar DNA-binding and transactivating activities. We further find that the POU domain is minimally required for these activities. Consequently, we show that all these Brn3 proteins have a similar ability to promote development of ganglion cells when ectopically expressed in retinal progenitors. During chick retinogenesis, cBrn3c instead of cBrn3b exhibits a spatial and temporal expression pattern characteristic of ganglion cell genesis and its misexpression can also increase ganglion cell production. Based on these data, we propose that all Brn3 factors are capable of promoting retinal ganglion cell development, and that this potential may be limited by the order of expression in vivo.