PMID- 21693522 OWN - NLM STAT- MEDLINE DCOM- 20110909 LR - 20211020 IS - 1477-9129 (Electronic) IS - 0950-1991 (Print) IS - 0950-1991 (Linking) VI - 138 IP - 14 DP - 2011 Jul TI - How to make stripes: deciphering the transition from non-periodic to periodic patterns in Drosophila segmentation. PG - 3067-78 LID - 10.1242/dev.062141 [doi] AB - 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. FAU - Schroeder, Mark D AU - Schroeder MD AD - Laboratory of Developmental Neurogenetics, Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. FAU - Greer, Christina AU - Greer C FAU - Gaul, Ulrike AU - Gaul U LA - eng GR - R21 GM066434/GM/NIGMS NIH HHS/United States GR - R33 GM066434/GM/NIGMS NIH HHS/United States GR - GM066434/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - England TA - Development JT - Development (Cambridge, England) JID - 8701744 RN - 0 (DNA-Binding Proteins) RN - 0 (Drosophila Proteins) RN - 0 (Fushi Tarazu Transcription Factors) RN - 0 (Homeodomain Proteins) RN - 0 (Nuclear Proteins) RN - 0 (Opa protein, Drosophila) RN - 0 (Transcription Factors) RN - 0 (ftz protein, Drosophila) RN - 0 (run protein, Drosophila) SB - IM MH - Animals MH - Animals, Genetically Modified MH - Body Patterning/*physiology MH - DNA-Binding Proteins/metabolism MH - Drosophila/*embryology MH - Drosophila Proteins/metabolism MH - Embryo, Nonmammalian/anatomy & histology/*embryology MH - Fushi Tarazu Transcription Factors/metabolism MH - Gene Expression Regulation, Developmental/*physiology MH - Genotype MH - Homeodomain Proteins/metabolism MH - In Situ Hybridization MH - Nuclear Proteins/metabolism MH - Periodicity MH - Transcription Factors/metabolism PMC - PMC3119311 EDAT- 2011/06/23 06:00 MHDA- 2011/09/10 06:00 PMCR- 2012/07/15 CRDT- 2011/06/23 06:00 PHST- 2011/06/23 06:00 [entrez] PHST- 2011/06/23 06:00 [pubmed] PHST- 2011/09/10 06:00 [medline] PHST- 2012/07/15 00:00 [pmc-release] AID - 138/14/3067 [pii] AID - 10.1242/dev.062141 [doi] PST - ppublish SO - Development. 2011 Jul;138(14):3067-78. doi: 10.1242/dev.062141.