Miller Adam C, Lyons Eric L, Herman Tory G
Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA.
Curr Biol. 2009 Aug 25;19(16):1378-83. doi: 10.1016/j.cub.2009.06.042. Epub 2009 Jul 23.
Lateral inhibition mediated by Delta/Notch (Dl/N) signaling is used throughout development to limit the number of initially equivalent cells that adopt a particular fate. Although adjacent cells express both Dl ligand and N receptor, signaling between them ultimately occurs in only one direction. Classically, this has been explained entirely by feedback: activated N can downregulate Dl, amplifying even slight asymmetries in the Dl or N activities of adjacent cells. Here, however, we present an example of lateral inhibition in which unidirectional signaling depends instead on Dl's ability to inhibit N within the same cell, a phenomenon known as cis-inhibition. By genetically manipulating individual R1/R6/R7 photoreceptor precursors in the Drosophila eye, we show that loss of Dl-mediated cis-inhibition reverses the direction of lateral signaling. Based on our finding that Dl in R1/R6s requires endocytosis to trans-activate but not to cis-inhibit N, we reexamine previously published data from other examples of lateral inhibition. We conclude that cis-inhibition generally influences the direction of Dl/N signaling and should therefore be included in standard models of lateral inhibition.
由Delta/Notch（Dl/N）信号介导的侧向抑制在整个发育过程中用于限制最初具有同等潜能、最终分化为特定命运的细胞数量。虽然相邻细胞同时表达Dl配体和N受体，但它们之间的信号传递最终仅在一个方向上发生。传统上，这完全是通过反馈来解释的：激活的N可以下调Dl，放大相邻细胞中Dl或N活性的微小不对称性。然而，在此我们展示了一个侧向抑制的例子，其中单向信号传递并非如此，而是依赖于Dl在同一细胞内抑制N的能力，这一现象称为顺式抑制。通过对果蝇眼中单个R1/R6/R7光感受器前体细胞进行基因操作，我们发现Dl介导的顺式抑制的缺失会逆转侧向信号的方向。基于我们的发现，即R1/R6细胞中的Dl需要内吞作用来反式激活而非顺式抑制N，我们重新审视了先前发表的来自其他侧向抑制例子的数据。我们得出结论，顺式抑制通常会影响Dl/N信号的方向，因此应纳入侧向抑制的标准模型中。
