Notch signaling via Hey1 and Id2b regulates Müller glia's regenerative response to retinal injury.
Notch signaling via Hey1 and Id2b regulates Müller glia's regenerative response to retinal injury.
复制标题
Notch信号通过HEY1和ID2B调节MüllerGlia对视网膜损伤的再生反应。
作者：
Sahu A;Devi S;Jui J;Goldman D
斑马鱼Müller神经胶质（MG）通过抑制Notch信号传导并产生用于视网膜修复的祖细胞来响应视网膜损伤。为了使MG参与再生响应（MG的损伤响应阈值），必须超过损伤衍生信号的一定阈值。全视网膜Notch抑制扩大了损伤反应性MG在局灶性损伤部位的区域，表明Notch信号传导调节MG的损伤反应阈值。我们发现Notch信号增强了未损伤视网膜中再生相关基因亚组的染色质可及性和基因表达。两个Notch效应基因，hey 1和id 2b，被确定为反映Notch信号通路的分叉，并差异调节MG的损伤反应阈值和MG衍生祖细胞的增殖。此外，Notch信号传导组分基因在受损视网膜中的抑制表明Dll 4、Dlb和Notch 3在MG中调节Notch信号传导中的作用，并且上位性实验证实Dll 4/Dlb-Notch 3-Hey 1/Id 2b信号传导途径调节MG的损伤反应阈值和增殖。
Zebrafish Müller glia (MG) respond to retinal injury by suppressing Notch signaling and producing progenitors for retinal repair. A certain threshold of injury-derived signal must be exceeded in order to engage MG in a regenerative response (MG’s injury-response threshold). Pan-retinal Notch inhibition expands the zone of injury-responsive MG at the site of focal injury, suggesting that Notch signaling regulates MG’s injury-response threshold. We found that Notch signaling enhanced chromatin accessibility and gene expression at a subset of regeneration-associated genes in the uninjured retina. Two Notch effector genes, hey1 and id2b, were identified that reflect bifurcation of the Notch signaling pathway, and differentially regulate MG’s injury-response threshold and proliferation of MG-derived progenitors. Furthermore, Notch signaling component gene repression in the injured retina suggests a role for Dll4, Dlb, and Notch3 in regulating Notch signaling in MG and epistasis experiments confirm that the Dll4/Dlb-Notch3-Hey1/Id2b signaling pathway regulates MG’s injury-response threshold and proliferation.
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影响因子：
--
作者：
Alvarez Y;Cederlund ML;Cottell DC;Bill BR;Ekker SC;Torres-Vazquez J;Weinstein BM;Hyde DR;Vihtelic TS;Kennedy BN
通讯作者：
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5.3
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