Université Côte d'Azur, CNRS, Inserm, iBV, Nice, France.
Sci Rep. 2019 Jul 10;9(1):9958. doi: 10.1038/s41598-019-46067-1.
The morphogenesis of the nervous system requires coordinating the specification and differentiation of neural precursor cells, the establishment of neuroepithelial tissue architecture and the execution of specific cellular movements. How these aspects of neural development are linked is incompletely understood. Here we inactivate a major regulator of embryonic neurogenesis - the Delta/Notch pathway - and analyze the effect on zebrafish central nervous system morphogenesis. While some parts of the nervous system can establish neuroepithelial tissue architecture independently of Notch, Notch signaling is essential for spinal cord morphogenesis. In this tissue, Notch signaling is required to repress neuronal differentiation and allow thereby the emergence of neuroepithelial apico-basal polarity. Notch-mediated suppression of neurogenesis is also essential for the execution of specific morphogenetic movements of zebrafish spinal cord precursor cells. In the wild-type neural tube, cells divide at the organ midline to contribute one daughter cell to each organ half. Notch signaling deficient animals fail to display this behavior and therefore form a misproportioned spinal cord. Taken together, our findings show that Notch-mediated suppression of neurogenesis is required to allow the execution of morphogenetic programs that shape the zebrafish spinal cord.
神经系统的形态发生需要协调神经前体细胞的特化和分化、神经上皮组织架构的建立以及特定细胞运动的执行。这些神经发育的方面是如何联系在一起的还不完全清楚。在这里，我们使一种主要的胚胎神经发生调节剂 - Delta/Notch 途径失活，并分析其对斑马鱼中枢神经系统形态发生的影响。虽然神经系统的某些部分可以独立于 Notch 建立神经上皮组织架构，但 Notch 信号对于脊髓形态发生是必不可少的。在这个组织中，Notch 信号被用来抑制神经元分化，从而产生神经上皮的顶-基底极性。Notch 介导的神经发生抑制对于执行斑马鱼脊髓前体细胞的特定形态发生运动也是必不可少的。在野生型神经管中，细胞在器官中线处分裂，为每个器官半部分贡献一个子细胞。 Notch 信号缺陷动物未能表现出这种行为，因此形成了不成比例的脊髓。总之，我们的研究结果表明，Notch 介导的神经发生抑制对于执行塑造斑马鱼脊髓的形态发生程序是必要的。
