How to make stripes: deciphering the transition from non-periodic to periodic patterns inDrosophilasegmentation

Abstract

SUMMARYThe 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.

Global analysis of Drosophila Cys2-His2 zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants

“…Recognition motifs for TFs within a common regulatory network can be used to computationally identify putative cis-regulatory modules and define the regulatory role of each member (Kazemian et al 2010;Kaplan et al 2011;Schroeder et al 2011;Marbach et al 2012;Neph et al 2012). Previously, we validated B1H-defined recognition motifs for TFs involved in anterior-posterior axis segmentation by demonstrating their ability to discriminate genomic regions corresponding to ChIP-chip peaks for each factor from randomly chosen noncoding regions (Kazemian et al 2010).…”

P-value-based regulatory motif discovery using positional weight matrices

“…We obtained the sequences of 54 hand-curated cis-regulatory modules for segmentation in the early D. melanogaster embryo (Methods) that are all primarily targeted by maternal and gap genes (Schroeder et al 2004(Schroeder et al , 2011). Since we expect functional binding sites to be more conserved than background, we used the 13 most related species of the UCSC 15-way multiple sequence alignments …”

Speed regulation of genetic cascades allows for evolvability in the body plan specification of insects

“…Insects differ in the number of fates specified in the blastoderm vs. germband. In short-germ insects [e.g., the grasshopper Schistocerca americana (21)], most fates form in the germband, while, in long-germ insects [e.g., the fruit fly Drosophila melanogaster (22) and the beetle Callosobruchus maculatus (23)], most fates form in the blastoderm. Intermediate-germ insects lie somewhere between those two extreme cases.…”