A damped oscillator imposes temporal order on posterior gap gene expression in Drosophila

This is the author accepted manuscript. The final version is available from Public Library of Science via the DOI in this recordInsects determine their body segments in two different ways. Short-germband insects, such as the flour beetle Tribolium castaneum, use a molecular clock to establish segments sequentially. In contrast, long-germband insects, such as the vinegar fly Drosophila melanogaster, determine all segments simultaneously through a hierarchical cascade of gene regulation. Gap genes constitute the first layer of the Drosophila segmentation gene hierarchy, downstream of maternal gradients such as that of Caudal (Cad). We use data-driven mathematical modelling and phase space analysis to show that shifting gap domains in the posterior half of the Drosophila embryo are an emergent property of a robust damped oscillator mechanism, suggesting that the regulatory dynamics underlying long- and short-germband segmentation are much more similar than previously thought. In Tribolium, Cad has been proposed to modulate the frequency of the segmentation oscillator. Surprisingly, our simulations and experiments show that the shift rate of posterior gap domains is independent of maternal Cad levels in Drosophila. Our results suggest a novel evolutionary scenario for the short- to long-germband transition and help explain why this transition occurred convergently multiple times during the radiation of the holometabolan insects.MINECO (grant number BFU2009-10184/BFU2012-33775/SEV-2012-0208). BFU2009-10184/BFU2012-33775 were 'Plan Nacional' grants to the group of JJ. SEV-2012-0208 was an 'Centro de Excelencia Severo Ochoa 2013- 2017' award to the CRG. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. European Commission http://www.biopredyn.eu (grant number FP7/KBBE-2011/5/289434). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. MEC-EMBL Agreement for the EMBL/CRG Research Unit in Systems Biology (grant number). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. La Caixa Savings Bank (grant number). PhD Fellowship received by BV at the CRG/EMBL Research Unit in Systems Biology. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. KLI Klosterneuburg (grant number). PhD Writing-up & Postdoctoral Fellowships to BV. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Wissenschaftskolleg zu Berlin (Wiko) (grant number). Ten-month fellowship 2014/15 to JJ, as well as a "College for Life Science" fellowship 2015 to AC. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Center for Systems Biology Dresden (CSBD)/Max Planck Gesellschaft (grant number). Four-month visiting stipend to JJ. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript