Graduate Institute of Biomedical Sciences, School of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Dev Biol. 2013 Mar 1;375(1):1-12. doi: 10.1016/j.ydbio.2013.01.007. Epub 2013 Jan 15.
Delta/notch-like epidermal growth factor (EGF)-related receptor (DNER) is a single-pass transmembrane protein found to be a novel ligand in the Notch signaling pathway. Its function was previously characterized in the developing cerebellum and inner ear hair cells. In this study, we isolated a zebrafish homolog of DNER and showed that this gene is expressed in the developing nervous system. Overexpression of dner or the intracellular domain of dner was sufficient to inhibit the proliferation of neural progenitors and induce neuronal and glial differentiation. In contrast, the knockdown of endogenous Dner expression using antisense morpholino oligonucleotides increased the proliferation of neural progenitors and maintained neural cells in a progenitor status through inhibition of neuronal and glial differentiation. Through analysis of the antagonistic effect on the Delta ligand and the role of the potential downstream mediator Deltex1, we showed that Dner acts in Notch-dependent and Notch-independent manner. This is the first study to demonstrate a role for Dner in neural progenitors and neuronal differentiation and provides new insights into mediation of neuronal development and differentiation by the Notch signaling pathway.
Delta/notch 样表皮生长因子（EGF）相关受体（DNER）是一种单次跨膜蛋白，被发现是 Notch 信号通路中的一种新型配体。其功能先前在发育中的小脑和内耳毛细胞中得到了表征。在这项研究中，我们分离了一种斑马鱼 DNER 同源物，并表明该基因在发育中的神经系统中表达。过表达 dner 或 dner 的细胞内结构域足以抑制神经前体细胞的增殖，并诱导神经元和神经胶质分化。相比之下，使用反义形态发生素寡核苷酸敲低内源性 Dner 表达会增加神经前体细胞的增殖，并通过抑制神经元和神经胶质分化将神经细胞维持在祖细胞状态。通过对 Delta 配体的拮抗作用和潜在下游介体 Deltex1 的作用分析，我们表明 Dner 以 Notch 依赖和非依赖的方式发挥作用。这是首次证明 Dner 在神经前体细胞和神经元分化中的作用的研究，并为 Notch 信号通路介导的神经元发育和分化提供了新的见解。
