Proneural gene self-stimulation in neural precursors:: an essential mechanism for sense organ development that is regulated by Notch signaling
Proneural gene self-stimulation in neural precursors:: an essential mechanism for sense organ development that is regulated by Notch signaling
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DOI：
10.1101/gad.12.13.2036
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发表时间：
1998-07-01
影响因子：
10.5
通讯作者：
Modolell, J
中科院分区：
文献类型：
--
作者：
Culí, J;Modolell, J
为了了解外胚层细胞对神经命运的获得，我们分析了果蝇神经承诺的一个非常早期的迹象，即在成为感觉器官母细胞(SMC)的细胞中，无毛-鳞状复合体(AS-C)神经蛋白的特异性积累。我们已经鉴定了一种AS-C增强子，它特异性地指导SMC中的表达，这种增强子促进这些细胞中Scute蛋白的积累，在缺乏其他BS-C基因的情况下，这是感觉器官发育所必需的事件。种间序列比较和定点突变表明，存在几个增强基因作用所必需的保守基序，其中一些基序与原神经蛋白结合。这些和其他数据表明，增强子介导Scute自我刺激，尽管只有在存在额外的激活因子时，这些激活因子很可能与使人想起核因子-kappa B结合位点的保守基序相互作用。邻近SMC的细胞不会获得神经命运，因为Notch信号通路效应器是bHLH蛋白裂解的增强子，可能通过拮抗NF-kappa B样因子或原神经蛋白的增强子的作用来阻断这种神经基因自刺激环。这些数据表明了一种SMC承诺的机制。
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 BS-C genes. Interspecific sequence comparisons and site-directed mutagenesis shaw 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-kappa B-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-kappa B-like factors or the proneural proteins. These data suggest a mechanism for SMC committment.