Department of Physics, University of Michigan, Ann Arbor, MI 48109-1040, USA.
Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):11145-50. doi: 10.1073/pnas.1015302108. Epub 2011 Jun 20.
The crystalline photoreceptor lattice in the Drosophila eye is a paradigm for pattern formation during development. During eye development, activation of proneural genes at a moving front adds new columns to a regular lattice of R8 photoreceptors. We present a mathematical model of the governing activator-inhibitor system, which indicates that the dynamics of positive induction play a central role in the selection of certain cells as R8s. The "switch and template" patterning mechanism we observe is mathematically very different from the well-known Turing instability. Unlike a standard lateral inhibition model, our picture implies that R8s are defined before the appearance of the complete group of proneural cells. The model reproduces the full time course of proneural gene expression and accounts for specific features of the refinement of proneural groups that had resisted explanation. It moreover predicts that perturbing the normal template can lead to eyes containing stripes of R8 cells. We observed these stripes experimentally after manipulation of the Notch and scabrous genes. Our results suggest an alternative to the generally assumed mode of operation for lateral inhibition during development; more generally, they hint at a broader role for bistable switches in the initial establishment of patterns as well as in their maintenance.
果蝇眼睛中的晶状光感受器晶格是发育过程中模式形成的典范。在眼睛发育过程中，在移动前沿激活神经前基因会向 R8 光感受器的规则晶格添加新的列。我们提出了一个支配激活剂-抑制剂系统的数学模型，该模型表明正诱导的动力学在选择某些细胞作为 R8 方面起着核心作用。我们观察到的“开关和模板”模式形成机制在数学上与众所周知的 Turing 不稳定性有很大的不同。与标准的侧向抑制模型不同，我们的图像表明 R8 是在出现完整的神经前细胞群之前定义的。该模型再现了神经前基因表达的完整时间过程，并解释了以前难以解释的神经前细胞群细化的具体特征。此外，它还预测，扰乱正常模板会导致眼睛中出现 R8 细胞条纹。在操纵 Notch 和粗糙基因后，我们在实验中观察到了这些条纹。我们的结果为发育过程中侧向抑制的一般假设模式提供了替代方案；更普遍地说，它们暗示双稳态开关在模式的初始建立以及其维持中可能发挥更广泛的作用。
