Multiple intrinsic factors act in concert with Lhx2 to direct retinal gliogenesis.
Multiple intrinsic factors act in concert with Lhx2 to direct retinal gliogenesis.
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DOI：
10.1038/srep32757
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发表时间：
2016-09-08
影响因子：
4.6
通讯作者：
Blackshaw S
中科院分区：
文献类型：
--
作者：
de Melo J;Clark BS;Blackshaw S
Müler glia(MG)是脊椎动物视网膜中的主要胶质细胞类型。最近的工作已经确定LIM同源结构域因子编码基因LHX2对于晚期视网膜前体细胞(RPC)的Notch信号和MG分化都是必需的。然而，LHX2与MG分化的其他内在调节因子的相互作用程度尚不清楚。我们通过调查在野生型和LHX2缺陷的RPC中过表达的多种转录调节因子的影响来研究这个问题，这些转录调节因子已知或假设可以控制MG的形成。我们观察到，N1ICD电穿孔诱导的结构性升高的Notch信号抑制了野生型动物的胶质形成，但挽救了LHX2缺陷视网膜的MG发育。Nfia的电穿孔促进了类MG放射状细胞的形成，但不促进MG分子标志物的表达。Plagl1和Sox9不能诱导野生型动物的胶质形成，但在LHX2缺失的细胞中激活了Müler标记P27Kip1的表达。最后，Sox2、Sox8和Sox9促进LHX2缺陷细胞中无长突细胞的形成，但在野生型视网膜中不能。这些发现表明，个别胶质生成因子的过度表达通常只调节一小部分典型的MG标志物，这些影响是由LHX2不同地调节的。
Müller glia (MG) are the principal glial cell type in the vertebrate retina. Recent work has identified the LIM homeodomain factor encoding gene Lhx2 as necessary for both Notch signaling and MG differentiation in late-stage retinal progenitor cells (RPCs). However, the extent to which Lhx2 interacts with other intrinsic regulators of MG differentiation is unclear. We investigated this question by investigating the effects of overexpression of multiple transcriptional regulators that are either known or hypothesized to control MG formation, in both wildtype and Lhx2-deficient RPCs. We observe that constitutively elevated Notch signaling, induced by N1ICD electroporation, inhibited gliogenesis in wildtype animals, but rescued MG development in Lhx2-deficient retinas. Electroporation of Nfia promoted the formation of cells with MG-like radial morphology, but did not drive expression of MG molecular markers. Plagl1 and Sox9 did not induce gliogenesis in wildtype animals, but nonetheless activated expression of the Müller marker P27Kip1 in Lhx2-deficient cells. Finally, Sox2, Sox8, and Sox9 promoted amacrine cell formation in Lhx2-deficient cells, but not in wildtype retinas. These findings demonstrate that overexpression of individual gliogenic factors typically regulates only a subset of characteristic MG markers, and that these effects are differentially modulated by Lhx2.
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DOI：
10.1073/pnas.1107488109
发表时间：
2012-03-20
影响因子：
11.1
作者：
de Melo, Jimmy;Miki, Katsuaki;Blackshaw, Seth
通讯作者：
Blackshaw, Seth
影响因子：
5.3
作者：
Bernardos, Rebecca L.;Barthel, Linda K.;Raymond, Pamela A.
通讯作者：
Raymond, Pamela A.
影响因子：
4.4
作者：
Lin, Ya-Ping;Ouchi, Yasuo;Watanabe, Sumiko
通讯作者：
Watanabe, Sumiko
影响因子：
2.7
作者：
Lee, HY;Wroblewski, E;Brown, NL
通讯作者：
Brown, NL
DOI：
10.1073/pnas.0807453105
发表时间：
2008-12-09
影响因子：
11.1
作者：
Karl, Mike O.;Hayes, Susan;Reh, Thomas A.
通讯作者：
Reh, Thomas A.