Centre for Mathematics and Physics in the Life Sciences and Experimental Biology, London, WC1E 6BT, UK.
Dev Cell. 2010 Jul 20;19(1):78-89. doi: 10.1016/j.devcel.2010.06.006.
The organization of bristles on the Drosophila notum has long served as a popular model of robust tissue patterning. During this process, membrane-tethered Delta activates intracellular Notch signaling in neighboring epithelial cells, which inhibits Delta expression. This induces lateral inhibition, yielding a pattern in which each Delta-expressing mechanosensory organ precursor cell in the epithelium is surrounded on all sides by cells with active Notch signaling. Here, we show that conventional models of Delta-Notch signaling cannot account for bristle spacing or the gradual refinement of this pattern. Instead, the pattern refinement we observe using live imaging is dependent upon dynamic, basal actin-based filopodia and can be quantitatively reproduced by simulations of lateral inhibition incorporating Delta-Notch signaling by transient filopodial contacts between nonneighboring cells. Significantly, the intermittent signaling induced by these filopodial dynamics generates a type of structured noise that is uniquely suited to the generation of well-ordered, tissue-wide epithelial patterns.
果蝇背部刚毛的组织排列长期以来一直是稳健组织模式形成的一个受欢迎的模型。在此过程中，膜结合的 Delta 在相邻上皮细胞中激活细胞内 Notch 信号通路，从而抑制 Delta 的表达。这诱导了侧向抑制，产生了一种模式，其中上皮组织中的每个表达 Delta 的机械感觉器官前体细胞都被具有活性 Notch 信号通路的细胞包围在所有侧面。在这里，我们表明，Delta-Notch 信号的传统模型不能解释刚毛间距或这种模式的逐渐细化。相反，我们通过实时成像观察到的模式细化依赖于动态的、基于基底肌动蛋白的丝状伪足，并且可以通过模拟侧向抑制来定量再现，该模拟通过非相邻细胞之间短暂的丝状伪足接触来整合 Delta-Notch 信号。重要的是，这些丝状伪足动力学诱导的间歇性信号产生了一种结构噪声，特别适合于生成有序的、全组织上皮模式。
