title: Segmenting the fly embryo: a logical analysis of the pair-rule cross-regulatory module.
abstract: This manuscript reports a dynamical analysis of the pair-rule cross-regulatory module controlling segmentation in Drosophila melanogaster. We propose a logical model accounting for the ability of the pair-rule module to determine the formation of alternate juxtaposed Engrailed- and Wingless-expressing cells that form the (para)segmental boundaries. This module has the intrinsic capacity to generate four distinct expression states, each characterized by the expression of a particular combination of pair-rule genes or expression mode. The selection of one of these expression modes depends on the maternal and gap inputs, but also crucially on cross-regulations among pair-rule genes. The latter are instrumental in the interpretation of the maternal-gap pre-pattern. Our logical model allows the qualitative reproduction of the patterns of pair-rule gene expressions corresponding to the wild type situation, to loss-of-function and cis-regulatory mutations, and to ectopic pair-rule expressions. Furthermore, this model provides a formal explanation for the morphogenetic role of the initial bell-shaped expression of the gene even-skipped, i.e. for the distinct effects of different levels of the Even-skipped protein on its target pair-rule genes. It also accounts for the requirement of Even-skipped for the formation of all Engrailed-stripes. Finally, it provides new insights into the roles and evolutionary origins of the apparent redundancies in the regulatory architecture of the pair-rule module.
authors.affiliation: Centro de Investigaciones Biológicas, Velázquez 144, 28006 Madrid, Spain. lsanchez@cib.csic.es
authors.forename: Lucas
authors.initials: L
authors.lastname: Sánchez
authors.forename: Denis
authors.initials: D
authors.lastname: Thieffry
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D008957:Models, Genetic