Morel V, Schweisguth F
Ecole Normale Supérieure, Centre National de la Recherche Scientifique (CNRS) Action Thématique Incitative sur Programme et Equipe (ATIPE) Unité Mixte de Recherche (UMR) 8544, 75230 Paris Cedex 05, France.
Genes Dev. 2000 Feb 1;14(3):377-88.
Notch signal transduction appears to involve the ligand-induced intracellular processing of Notch, and the formation of a processed Notch-Suppressor of Hairless complex that binds DNA and activates the transcription of Notch target genes. This suggests that loss of either Notch or Su(H) activities should lead to similar cell fate changes. However, previous data indicate that, in the Drosophila blastoderm embryo, mesectoderm specification requires Notch but not Su(H) activity. The determination of the mesectodermal fate is specified by Single-minded (Sim), a transcription factor expressed in a single row of cells abutting the mesoderm. The molecular mechanisms by which the dorsoventral gradient of nuclear Dorsal establishes the single-cell wide territory of sim expression are not fully understood. We have found that Notch activity is required for sim expression in cellularizing embryos. In contrast, at this stage, Su(H) has a dual function. Su(H) activity was required to up-regulate sim expression in the mesectoderm, and to prevent the ectopic expression of sim dorsally in the neuroectoderm. We have shown that repression of sim transcription by Su(H) is direct and independent of Notch activity. Conversely, activation of sim transcription by Notch requires the Su(H)-binding sites. Thus, Notch signalling appears to relieve the repression exerted by Su(H) and to up-regulate sim transcription in the mesectoderm. We propose a model in which repression by Su(H) and derepression by Notch are essential to allow for the definition of a single row of mesectodermal cells in the blastoderm embryo.
Notch信号转导似乎涉及配体诱导的Notch细胞内加工,以及形成一种加工后的Notch-无毛抑制因子复合物,该复合物结合DNA并激活Notch靶基因的转录。这表明Notch或Su(H)活性的丧失应导致相似的细胞命运变化。然而,先前的数据表明,在果蝇胚盘胚胎中,中胚层的特化需要Notch活性,但不需要Su(H)活性。中胚层命运的决定由单 minded(Sim)指定,Sim是一种转录因子,在与中胚层相邻的单列细胞中表达。核背侧蛋白的背腹梯度建立sim表达的单细胞宽区域的分子机制尚不完全清楚。我们发现,在细胞化胚胎中,sim表达需要Notch活性。相比之下,在这个阶段,Su(H)具有双重功能。Su(H)活性对于上调中胚层中sim的表达以及防止sim在神经外胚层背侧异位表达是必需的。我们已经表明,Su(H)对sim转录的抑制是直接的,并且独立于Notch活性。相反,Notch对sim转录的激活需要Su(H)结合位点。因此,Notch信号似乎解除了Su(H)施加的抑制,并上调了中胚层中sim的转录。我们提出了一个模型,其中Su(H)的抑制和Notch的去抑制对于在胚盘胚胎中定义单列中胚层细胞至关重要。