Laboratory of Developmental Neurogenetics, Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Development. 2011 Jul;138(14):3067-78. doi: 10.1242/dev.062141.
The generation of metameric body plans is a key process in development. In Drosophila segmentation, periodicity is established rapidly through the complex transcriptional regulation of the pair-rule genes. The 'primary' pair-rule genes generate their 7-stripe expression through stripe-specific cis-regulatory elements controlled by the preceding non-periodic maternal and gap gene patterns, whereas 'secondary' pair-rule genes are thought to rely on 7-stripe elements that read off the already periodic primary pair-rule patterns. Using a combination of computational and experimental approaches, we have conducted a comprehensive systems-level examination of the regulatory architecture underlying pair-rule stripe formation. We find that runt (run), fushi tarazu (ftz) and odd skipped (odd) establish most of their pattern through stripe-specific elements, arguing for a reclassification of ftz and odd as primary pair-rule genes. In the case of run, we observe long-range cis-regulation across multiple intervening genes. The 7-stripe elements of run, ftz and odd are active concurrently with the stripe-specific elements, indicating that maternal/gap-mediated control and pair-rule gene cross-regulation are closely integrated. Stripe-specific elements fall into three distinct classes based on their principal repressive gap factor input; stripe positions along the gap gradients correlate with the strength of predicted input. The prevalence of cis-elements that generate two stripes and their genomic organization suggest that single-stripe elements arose by splitting and subfunctionalization of ancestral dual-stripe elements. Overall, our study provides a greatly improved understanding of how periodic patterns are established in the Drosophila embryo.
体型分节的产生是发育过程中的一个关键过程。在果蝇的体节形成过程中,周期性是通过对成对规则基因的复杂转录调控迅速建立起来的。“初级”成对规则基因通过受前导非周期性母源和缺口基因模式控制的条纹特异性顺式调控元件,产生其 7 条纹表达,而“次级”成对规则基因被认为依赖于能够读取已经周期性的初级成对规则模式的 7 条纹元件。我们使用计算和实验相结合的方法,对成对规则条纹形成的调控结构进行了全面的系统水平研究。我们发现 runt(run)、fushi tarazu(ftz)和 odd skipped(odd)通过条纹特异性元件建立了它们的大部分模式,这表明 ftz 和 odd 被重新归类为初级成对规则基因。就 run 而言,我们观察到跨越多个中间基因的长距离顺式调控。run、ftz 和 odd 的 7 条纹元件与条纹特异性元件同时活跃,表明母源/缺口介导的控制和成对规则基因的交叉调控紧密结合。条纹特异性元件根据其主要的抑制性缺口因子输入分为三类;沿缺口梯度的条纹位置与预测输入的强度相关。生成两个条纹的顺式元件的普遍性及其基因组组织表明,单条纹元件是通过祖先双条纹元件的分裂和亚功能化产生的。总的来说,我们的研究极大地提高了我们对果蝇胚胎中周期性模式是如何建立的理解。