Apidianakis Y, Nagel A C, Chalkiadaki A, Preiss A, Delidakis C
Institute of Molecular Biology and Biotechnology, FORTH and Department of Biology, University of Crete, Box 1527, Heraklion GR-71 110, Greece.
Mech Dev. 1999 Aug;86(1-2):39-50. doi: 10.1016/s0925-4773(99)00099-4.
Intercellular signalling mediated by Notch proteins is crucial to many cell fate decisions in metazoans. Its profound effects on cell fate and proliferation require that a complex set of responses involving positive and negative signal transducers be orchestrated around each instance of signalling. In Drosophila the basic-helix-loop-helix (bHLH) repressor encoding genes of the E(spl) locus are induced by Notch signalling and mediate some of its effects, such as suppression of neural fate. Here we report on a novel family of Notch responsive genes, whose products appear to act as antagonists of the Notch signal in the process of adult sensory organ precursor singularization. They, too, reside in the E(spl) locus and comprise transcription units E(spl) m4 and E(spl) malpha. Overexpression of these genes causes downregulation of E(spl) bHLH expression accompanied by cell autonomous overcommitment of sensory organ precursors and tufting of bristles. Interestingly, negative regulation of the Notch pathway by overexpression of E(spl) m4 and malpha is specific to the process of sensory organ precursor singularization and does not impinge on other instances of Notch signalling.
由Notch蛋白介导的细胞间信号传导对于后生动物中许多细胞命运的决定至关重要。其对细胞命运和增殖的深远影响要求围绕每个信号实例精心编排一系列复杂的反应,这些反应涉及正、负信号转导器。在果蝇中,E(spl)位点的基本螺旋-环-螺旋(bHLH)阻遏物编码基因由Notch信号诱导,并介导其一些效应,如抑制神经命运。在此,我们报道了一个新的Notch反应基因家族,其产物在成虫感觉器官前体细胞的特化过程中似乎作为Notch信号的拮抗剂发挥作用。它们也位于E(spl)位点,包括转录单元E(spl) m4和E(spl) malpha。这些基因的过表达导致E(spl) bHLH表达下调,同时伴有感觉器官前体细胞的细胞自主过度特化和刚毛簇生。有趣的是,通过E(spl) m4和malpha的过表达对Notch途径的负调控仅限于感觉器官前体细胞特化过程,并不影响Notch信号传导的其他实例。