Baker N E, Yu S Y
Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Curr Biol. 1997 Feb 1;7(2):122-32. doi: 10.1016/s0960-9822(06)00056-x.
. Intercellular signals are major determinants of cell fate during development. Certain signals and receptors are important for many different cell-fate decisions, suggesting that cellular responses to similar signals change during development. Few transitions between such distinct cellular responses have been studied. The Drosophila genes Notch and hedgehog function during intracellular signaling at various stages of development. In the specific case of development of the Drosophila eye, expression of the proneural gene atonal is induced in response to Hedgehog signaling and then becomes subject to autoregulation. The receptor protein Notch has previously been reported to function in the selection of single founder photoreceptor cells (R8 cells) by inhibiting atonal expression. On this basis, complete elimination of Notch gene function would be expected to cause neural hyperplasia in the eye.
. Contrary to expectation, we detect a reduction in neural differentiation both in cells expressing a conditional Notch allele and in those lacking expression of either Notch or its ligand Delta. We show here that Notch signaling acts after the initial Hedgehog-driven expression of atonal to enhance proneural competence of the atonal-expressing cells and also to terminate their response to the Hedgehog signals. This occurs before the Notch-induced lateral inhibition of atonal expression within the same cells.
. Notch has sequentially opposite effects on the same cells, by first promoting and then inhibiting proneural gene function. This apparently paradoxical sequence of events has two possible consequences. Firstly, coupling of alternative cellular responses to the same receptor may prevent them from occurring simultaneously. Secondly, consecutive regulatory processes become temporally coupled, so that these events follow on from each other, without gaps or overlaps.
细胞间信号是发育过程中细胞命运的主要决定因素。某些信号和受体对许多不同的细胞命运决定都很重要，这表明细胞对相似信号的反应在发育过程中会发生变化。但很少有研究探讨这种不同细胞反应之间的转变。果蝇的Notch基因和刺猬索尼克基因在发育的各个阶段的细胞内信号传导过程中发挥作用。在果蝇眼睛发育的特定情况下，神经前体基因无调的表达是对刺猬索尼克信号的响应而被诱导的，然后进入自我调节阶段。此前有报道称，受体蛋白Notch通过抑制无调的表达，在单个感光细胞（R8细胞）的选择过程中发挥作用。基于此，预期完全消除Notch基因功能会导致眼睛中的神经增生。
与预期相反，我们发现在表达条件性Notch等位基因的细胞以及缺乏Notch或其配体Delta表达的细胞中，神经分化均减少。我们在此表明，Notch信号在无调最初由刺猬索尼克驱动表达之后起作用，以增强表达无调的细胞的神经前体能力，并终止它们对刺猬索尼克信号的反应。这发生在Notch诱导同一细胞内无调表达的侧向抑制之前。
Notch对同一细胞具有先后相反的作用，先是促进然后抑制神经前体基因功能。这一明显矛盾的事件序列可能有两个后果。首先，将不同的细胞反应与同一受体偶联可能会阻止它们同时发生。其次，连续的调节过程在时间上偶联，使得这些事件相继发生，没有间隙或重叠。
