Departments of Genetics and Medical Genetics, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
PLoS One. 2013 Jul 4;8(7):e67789. doi: 10.1371/journal.pone.0067789. Print 2013.
The Notch gene encodes an evolutionarily conserved cell surface receptor that generates regulatory signals based on interactions between neighboring cells. In Drosophila embryos it is normally expressed at a low level due to strong negative regulation. When this negative regulation is abrogated neurogenesis in the ventral region is suppressed, the development of lateral epidermis is severely disrupted, and the dorsal aminoserosa is expanded. Of these phenotypes only the anti-neurogenic phenotype could be linked to excess canonical Notch signaling. The other phenotypes were linked to high levels of Notch protein expression at the surface of cells in the lateral regions indicating that a non-canonical Notch signaling activity normally functions in these regions. Results of our studies reported here provide evidence. They show that Notch activities are inextricably linked to that of Pkc98E, the homolog of mammalian PKCδ. Notch and Pkc98E up-regulate the levels of the phosphorylated form of IκBCactus, a negative regulator of Toll signaling, and Mothers against dpp (MAD), an effector of Dpp signaling. Our data suggest that in the lateral regions of the Drosophila embryos Notch activity, in conjunction with Pkc98E activity, is used to form the slopes of the opposing gradients of Toll and Dpp signaling that specify cell fates along the dorso-ventral axis.
Notch 基因编码一种进化上保守的细胞表面受体，它根据相邻细胞之间的相互作用产生调节信号。在果蝇胚胎中，由于强烈的负调控，它通常表达水平较低。当这种负调控被废除时，腹侧区域的神经发生受到抑制，侧表皮的发育受到严重破坏，背侧氨基酸浆扩张。在这些表型中，只有抗神经发生表型可以与过量的经典 Notch 信号相关联。其他表型与细胞表面 Notch 蛋白表达水平升高有关，表明在这些区域通常存在非经典 Notch 信号活性。我们在这里报告的研究结果提供了证据。它们表明 Notch 活性与 Pkc98E（哺乳动物 PKCδ 的同源物）密切相关。Notch 和 Pkc98E 上调磷酸化形式的 IκBCactus（Toll 信号的负调节剂）和 Mothers against dpp（MAD，Dpp 信号的效应物）的水平。我们的数据表明，在果蝇胚胎的侧区，Notch 活性与 Pkc98E 活性一起用于形成 Toll 和 Dpp 信号的相反梯度的斜率，这些梯度沿背腹轴指定细胞命运。
