Mills Elizabeth A, Goldman Daniel
Molecular and Behavioral Neuroscience Institute, Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109.
Curr Pathobiol Rep. 2017 Dec;5(4):323-331. doi: 10.1007/s40139-017-0153-7. Epub 2017 Oct 6.
Notch signaling is an important component of retinal progenitor cell maintenance and MG specification during development, and its manipulation may be critical for allowing MG to re-enter the cell cycle and regenerate neurons in adults. In mammals, MG respond to retinal injury by undergoing a gliotic response rather than a regenerative one. Understanding the complexities of Notch signaling may allow for strategies that enhance regeneration over gliosis.
Notch signaling is regulated at multiple levels, and is interdependent with various other signaling pathways in both the receptor and ligand expressing cells. The precise spatial and temporal patterning of Notch components is necessary for proper retinal development. Regenerative species undergo a dynamic regulation of Notch signaling in MG upon injury, whereas non-regenerative species fail to productively regulate Notch.
Notch signaling is malleable, such that the altered composition of growth and transcription factors in the developing and mature retinas result in different Notch mediated responses. Successful regeneration will require the manipulation of the retinal environment to foster a dynamic rather than static regulation of Notch signaling in concert with other reprogramming and differentiation factors.
Notch信号通路是视网膜祖细胞在发育过程中维持和 Müller 胶质细胞（MG）特化的重要组成部分，对其进行调控可能对促使成年MG重新进入细胞周期并再生神经元至关重要。在哺乳动物中，MG对视网膜损伤的反应是发生胶质化反应而非再生反应。了解Notch信号通路的复杂性可能有助于制定增强再生而非胶质化的策略。
Notch信号通路在多个水平受到调控，并且在表达受体和配体的细胞中与其他多种信号通路相互依赖。Notch组件精确的时空模式对于视网膜的正常发育是必需的。再生物种在损伤后MG中经历Notch信号通路的动态调控，而非再生物种则无法有效调控Notch。
Notch信号通路具有可塑性，使得发育中和成熟视网膜中生长因子和转录因子组成的改变会导致不同的Notch介导的反应。成功的再生将需要对视网膜环境进行调控，以协同其他重编程和分化因子促进对Notch信号通路的动态而非静态调控。
