Kewalo Marine Laboratory, University of Hawaii, Honolulu, HI 96813, USA.
Dev Biol. 2012 Feb 15;362(2):295-308. doi: 10.1016/j.ydbio.2011.11.012. Epub 2011 Dec 1.
Notch signaling is among the oldest of known Metazoan signaling pathways and is used in a multitude of developmental contexts to effect cellular differentiation, specification and the maintenance of stem cell state. Here we report the isolation and expression of the canonical Notch signaling pathway in the early branching metazoan Nematostella vectensis (Anthozoa, Cnidaria) during embryonic and larval development. We have used pharmacological treatment, morpholino knockdown, and dominant negative misexpression experiments to demonstrate that Notch signaling acts to mediate cnidogenesis, the development of cnidarian-specific neural effecter cells. Notch signaling often results in the transcriptional activation of NvHes genes, a conserved family of bHLH transcription factors. A loss of Notch signaling through use of pharmacological inhibition or knock-down of the Notch effecter gene Suppressor of Hairless Su(H) similarly results in a loss of cnidocyte cell fate. We also provide evidence that Notch signaling is responsible for certain aspects of neurogenesis in developing N. vectensis planula in which disruption of Notch cleavage via the pharmacological agent DAPT results in increased expression of neural marker genes in vivo. This data suggests that Notch signaling acting on components of the developing nervous system is an ancient role of this pathway. The shared requirement of Notch signaling for the development of both cnidocytes and neurons further supports the hypothesis that cnidocytes and neurons share common origins as multifunctional sensory-effecter cells.
Notch 信号通路是已知的最古老的后生动物信号通路之一,在多种发育背景下用于影响细胞分化、特化和干细胞状态的维持。在这里,我们报告了经典 Notch 信号通路在早期分支后生动物 Nematostella vectensis(珊瑚纲,刺胞动物门)胚胎和幼虫发育过程中的分离和表达。我们已经使用药理学处理、mRNA 干扰和显性负突变体表达实验证明了 Notch 信号通路在刺细胞发生、刺胞动物特有的神经效应细胞发育中起作用。Notch 信号通路通常导致 NvHes 基因的转录激活,NvHes 基因是一个保守的 bHLH 转录因子家族。通过使用药理学抑制剂或 Notch 效应基因 Suppressor of Hairless Su(H) 的敲低来阻断 Notch 信号通路,同样会导致刺细胞命运的丧失。我们还提供了证据表明,Notch 信号通路负责发育中的 N. vectensis 浮浪幼虫神经发生的某些方面,通过药理学试剂 DAPT 对 Notch 切割的干扰导致体内神经标记基因的表达增加。这些数据表明,Notch 信号通路作用于发育中神经系统的成分是该途径的一个古老作用。Notch 信号通路对刺细胞和神经元发育的共同需求进一步支持了刺细胞和神经元作为多功能感觉-效应细胞具有共同起源的假说。