Simultaneous Requirements for Hes1 in Retinal Neurogenesis and Optic Cup-Stalk Boundary Maintenance
Simultaneous Requirements for Hes1 in Retinal Neurogenesis and Optic Cup-Stalk Boundary Maintenance
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DOI：
10.1523/jneurosci.2327-19.2020
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发表时间：
2020-02-12
影响因子：
5.3
通讯作者：
Brown, Nadean L.
中科院分区：
文献类型：
--
作者：
Bosze, Bernadett;Moon, Myung-Soon;Brown, Nadean L.
bHLH转录因子Hes 1是Notch信号通路的关键下游效应子。在胚胎发生期间，神经祖细胞以振荡模式表达低水平的Hes 1，而神经胶质脑边界区域（例如，峡部）具有高的、持续的Hes 1水平，其抑制神经元的命运。在这里，我们表明，在胚胎小鼠视网膜，视神经头和柄表达高Hes 1，与ONH构成的神经视网膜和胶质细胞之间的边界，最终线的视柄。使用具有不同时空表达的两个Cre驱动程序，我们有条件地使Hes 1失活，以描述在视网膜神经发生与视杯和柄的图案化过程中对该转录阻遏物的要求。在整个视网膜神经发生过程中，Hes 1维持增殖并阻断视网膜神经节细胞的形成，但令人惊讶的是，我们发现它也促进视锥光感受器的发生。在出生后的眼睛中，Hes 1与Rax-Cre失活导致双极神经元增加和Muller胶质细胞错位。我们的研究结果表明，Notch途径调节视锥细胞的发生比以前假设的更复杂，并揭示了Hes 1在维持视杯柄边界中的新作用。
The bHLH transcription factor Hes1 is a key downstream effector for the Notch signaling pathway. During embryogenesis neural progenitors express low levels of Hes1 in an oscillating pattern, whereas glial brain boundary regions (e.g., isthmus) have high, sustained Hes1 levels that suppress neuronal fates. Here, we show that in the embryonic mouse retina, the optic nerve head and stalk express high Hes1, with the ONH constituting a boundary between the neural retina and glial cells that ultimately line the optic stalk. Using two Cre drivers with distinct spatiotemporal expression we conditionally inactivated Hes1, to delineate the requirements for this transcriptional repressor during retinal neurogenesis versus patterning of the optic cup and stalk. Throughout retinal neurogenesis, Hes1 maintains proliferation and blocks retinal ganglion cell formation, but surprisingly we found it also promotes cone photoreceptor genesis. In the postnatal eye, Hes1 inactivation with Rax-Cre resulted in increased bipolar neurons and a mispositioning of Muller glia. Our results indicate that Notch pathway regulation of cone genesis is more complex than previously assumed, and reveal a novel role for Hes1 in maintaining the optic cup-stalk boundary.