Notch-Delta signaling is required for spatial patterning and Muller glia differentiation in the zebrafish retina
Notch-Delta signaling is required for spatial patterning and Muller glia differentiation in the zebrafish retina
复制标题
DOI：
10.1016/j.ydbio.2004.11.018
复制
发表时间：
2005-02-15
影响因子：
2.7
通讯作者：
Raymond, PA
中科院分区：
文献类型：
--
作者：
Bernardos, RL;Lentz, SI;Raymond, PA
Notch-Delta信号转导与脊椎动物视网膜中的几种替代功能模式有关。进一步研究这些功能。我们检查了斑马鱼胚胎的视网膜，其中双向Notch-Delta信号被思维炸弹（nub）突变灭活，这破坏了E3泛素连接酶的活性，或者被γ-分泌酶抑制剂处理灭活，这阻止了Notch和Delta的膜内蛋白水解。我们发现，失活Notch-Delta信号传导并不能阻止视网膜神经元的分化，但它确实破坏了视网膜上皮的顶部-基底和平面维度的空间模式。视网膜神经元分化，但其层状排列被破坏。光感受器分化正常启动，但其进展缓慢。虽然局限于正常视网膜的顶端视网膜表面，但视锥光感受器的平面组织被破坏：相同光谱亚型的视锥细胞聚集在一起，而不是规则地间隔开。与神经元相反，Muller胶质细胞未能分化，这表明Notch-Delta信号在胶质细胞发生中的指导作用。(C)2004年爱思唯尔公司All rights reserved.
Notch-Delta signaling has been implicated in several alternative modes of function in the vertebrate retina. To further investigate these functions. we examined retinas from zebrafish embryos in which bidirectional Notch-Delta signaling was inactivated either by the mind bomb (nub) mutation, which disrupts E3 ubiquitin ligase activity, or by treatment with gamma-secretase inhibitors, which prevent intramembrane proteolysis of Notch and Delta. We found that inactivating Notch-Delta signaling did not prevent differentiation of retinal neurons, but it did disrupt spatial patterning in both the apical-basal and planar dimensions of the retinal epithelium. Retinal neurons differentiated, but their laminar arrangement was disrupted. Photoreceptor differentiation was initiated normally, but its progression was slowed. Although confined to the apical retinal surface as in normal retinas, the planar organization of cone photoreceptors was disrupted: cones of the same spectral subtype were clumped rather than regularly spaced. In contrast to neurons, Muller glia failed to differentiate suggesting an instructive role for Notch-Delta signaling in gliogenesis. (C) 2004 Elsevier Inc. All rights reserved.