title: The spatiotemporal order of signaling events unveils the logic of development signaling.
abstract: Animals from worms and insects to birds and mammals show distinct body plans; however, the embryonic development of diverse body plans with tissues and organs within is controlled by a surprisingly few signaling pathways. It is well recognized that combinatorial use of and dynamic interactions among signaling pathways follow specific logic to control complex and accurate developmental signaling and patterning, but it remains elusive what such logic is, or even, what it looks like.
  
  
  
  We have developed a computational model for Drosophila eye development with innovated methods to reveal how interactions among multiple pathways control the dynamically generated hexagonal array of R8 cells. We obtained two novel findings. First, the coupling between the long-range inductive signals produced by the proneural Hh signaling and the short-range restrictive signals produced by the antineural Notch and EGFR signaling is essential for generating accurately spaced R8s. Second, the spatiotemporal orders of key signaling events reveal a robust pattern of lateral inhibition conducted by Ato-coordinated Notch and EGFR signaling to collectively determine R8 patterning. This pattern, stipulating the orders of signaling and comparable to the protocols of communication, may help decipher the well-appreciated but poorly defined logic of developmental signaling.
  
  
  
  The model is available upon request.
  
  
  
  hao.zhu@ymail.com
  
  
  
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Bioinformatics Section, Southern Medical University, Guangzhou 510515, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhu
authors.affiliation: School of Mathematical Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Markus R
authors.initials: MR
authors.lastname: Owen
authors.affiliation: MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK.
authors.forename: Yanlan
authors.initials: Y
authors.lastname: Mao
mesh_terms: D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins; D005123:Eye / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D008128:Logic; D051880:Receptors, Notch; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D051880:Receptors, Notch