title: How to make stripes: deciphering the transition from non-periodic to periodic patterns in Drosophila segmentation.
abstract: 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.
authors.affiliation: Laboratory of Developmental Neurogenetics, Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Schroeder
authors.forename: Christina
authors.initials: C
authors.lastname: Greer
authors.forename: Ulrike
authors.initials: U
authors.lastname: Gaul
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000196:embryology*; D051717:Fushi Tarazu Transcription Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005838:Genotype; D018398:Homeodomain Proteins / Q000378:metabolism; D017403:In Situ Hybridization; D009687:Nuclear Proteins / Q000378:metabolism; D010507:Periodicity; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; C085443:Opa protein, Drosophila; D014157:Transcription Factors; C497169:ftz protein, Drosophila; C080833:run protein, Drosophila