Culí J, Modolell J
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
Genes Dev. 1998 Jul 1;12(13):2036-47. doi: 10.1101/gad.12.13.2036.
To learn about the acquisition of neural fate by ectodermal cells, we have analyzed a very early sign of neural commitment in Drosophila, namely the specific accumulation of achaete-scute complex (AS-C) proneural proteins in the cell that becomes a sensory organ mother cell (SMC). We have characterized an AS-C enhancer that directs expression specifically in SMCs. This enhancer promotes Scute protein accumulation in these cells, an event essential for sensory organ development in the absence of other AS-C genes. Interspecific sequence comparisons and site-directed mutagenesis show the presence of several conserved motifs necessary for enhancer action, some of them binding sites for proneural proteins. These and other data indicate that the enhancer mediates scute self-stimulation, although only in the presence of additional activating factors, which most likely interact with conserved motifs reminiscent of NF-kappaB-binding sites. Cells neighboring the SMC do not acquire the neural fate because the Notch signaling pathway effectors, the Enhancer of split bHLH proteins, block this proneural gene self-stimulatory loop, possibly by antagonizing the action on the enhancer of the NF-kappaB-like factors or the proneural proteins. These data suggest a mechanism for SMC committment.
为了了解外胚层细胞如何获得神经命运，我们分析了果蝇中神经定向的一个非常早期的迹象，即在即将成为感觉器官母细胞（SMC）的细胞中achaete - scute复合体（AS - C）原神经蛋白的特异性积累。我们鉴定了一个AS - C增强子，它特异性地指导SMC中的表达。该增强子促进这些细胞中Scute蛋白的积累，在没有其他AS - C基因的情况下，这一事件对于感觉器官发育至关重要。种间序列比较和定点诱变显示存在增强子作用所必需的几个保守基序，其中一些是原神经蛋白的结合位点。这些以及其他数据表明，该增强子介导Scute自我刺激，尽管仅在存在额外激活因子的情况下，这些激活因子很可能与类似于NF - κB结合位点的保守基序相互作用。与SMC相邻的细胞不会获得神经命运，因为Notch信号通路效应器，即分裂bHLH蛋白增强子，可能通过拮抗NF - κB样因子或原神经蛋白对增强子的作用，阻断了这种原神经基因自我刺激环。这些数据提示了SMC定向的一种机制。
