Differential Expression of NF2 in Neuroepithelial Compartments Is Necessary for Mammalian Eye Development.
Differential Expression of NF2 in Neuroepithelial Compartments Is Necessary for Mammalian Eye Development.
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DOI：
10.1016/j.devcel.2017.11.011
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发表时间：
2018-01-08
影响因子：
11.8
通讯作者：
Kim JW
中科院分区：
文献类型：
--
作者：
Moon KH;Kim HT;Lee D;Rao MB;Levine EM;Lim DS;Kim JW
脊椎动物眼睛的视神经上皮连续体发育成三个差异生长的隔室-视网膜、睫状缘（CM）和视网膜色素上皮（RPE）。神经纤维蛋白2（Nf 2）在缓慢扩张的RPE和CM隔室中强烈表达，并且小鼠Nf 2的缺失导致这些隔室中的增生，复制在人类NF 2患者中观察到的眼部异常。通过Nf 2-Hippo信号通路的关键靶点雅普和Taz的杂合缺失，增生性眼表型在很大程度上受到抑制。我们进一步发现，除了CM中的雅普/Taz对Nf 2的反馈转录调节之外，RPE中的Mitf对Nf 2表达的激活和视网膜祖细胞中的Sox 2对Nf 2表达的抑制对于相应细胞群的差异生长是必需的。总之，我们的研究结果表明，Nf 2是一个关键的球员，协调视神经上皮隔室在脊椎动物眼睛发育的差异生长。Moon等人确定了小鼠眼睛中视神经上皮隔室差异生长的潜在机制。肿瘤抑制因子神经纤维蛋白2（Nf 2）在每个神经上皮隔室中的差异转录调节对于组织的差异生长是必要的。
The optic neuroepithelial continuum of vertebrate eye develops into three differentially growing compartments – the retina, ciliary margin (CM), and retinal pigment epithelium (RPE). The neurofibromin 2 (Nf2) is strongly expressed in slowly expanding RPE and CM compartments, and the loss of mouse Nf2 causes hyperplasia in these compartments, replicating the ocular abnormalities seen in human NF2 patients. The hyperplastic ocular phenotypes were largely suppressed by heterozygous deletion of Yap and Taz, key targets of the Nf2-Hippo signaling pathway. We further found that, in addition to feedback transcriptional regulation of Nf2 by Yap/Taz in the CM, activation of Nf2 expression by Mitf in the RPE and suppression by Sox2 in retinal progenitor cells are necessary for the differential growth of the corresponding cell populations. Together, our findings reveal that Nf2 is a key player that orchestrates the differential growth of optic neuroepithelial compartments during vertebrate eye development. Moon et al. identify a mechanism underlying the differential growth of optic neuroepithelial compartments in the mouse eye. Differential transcriptional regulation of the tumor suppressor Neurofibromin 2 (Nf2) in each neuroepithelial compartment is necessary for the differential growth of the tissue.
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DOI：
10.1126/science.1199010
发表时间：
2011-04-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Heallen T;Zhang M;Wang J;Bonilla-Claudio M;Klysik E;Johnson RL;Martin JF
通讯作者：
Martin JF
影响因子：
2.7
作者：
Fujimura, Naoko;Taketo, Makoto M.;Kozmik, Zbynek
通讯作者：
Kozmik, Zbynek
影响因子：
2.5
作者：
Akhmametyeva, Elena M.;Mihaylova, Maria M.;Chang, Long-Sheng
通讯作者：
Chang, Long-Sheng
影响因子：
8.8
作者：
Marcucci F;Murcia-Belmonte V;Wang Q;Coca Y;Ferreiro-Galve S;Kuwajima T;Khalid S;Ross ME;Mason C;Herrera E
通讯作者：
Herrera E
影响因子：
64.5
作者：
HODGKINSON, CA;MOORE, KJ;ARNHEITER, H
通讯作者：
ARNHEITER, H