title: JAK/STAT and Hox Dynamic Interactions in an Organogenetic Gene Cascade.
abstract: Organogenesis is controlled by gene networks activated by upstream selector genes. During development the gene network is activated stepwise, with a sequential deployment of successive transcription factors and signalling molecules that modify the interaction of the elements of the network as the organ forms. Very little is known about the steps leading from the early specification of the cells that form the organ primordium to the moment when a robust gene network is in place. Here we study in detail how a Hox protein induces during early embryogenesis a simple organogenetic cascade that matures into a complex gene network through the activation of feedback and feed forward interaction loops. To address how the network organization changes during development and how the target genes integrate the genetic information it provides, we analyze in Drosophila the induction of posterior spiracle organogenesis by the Hox gene Abdominal-B (Abd-B). Initially, Abd-B activates in the spiracle primordium a cascade of transcription factors and signalling molecules including the JAK/STAT signalling pathway. We find that at later stages STAT activity feeds back directly into Abd-B, initiating the transformation of the Hox cascade into a gene-network. Focusing on crumbs, a spiracle downstream target gene of Abd-B, we analyze how a modular cis regulatory element integrates the dynamic network information set by Abd-B and the JAK/STAT signalling pathway during development. We describe how a Hox induced genetic cascade transforms into a robust gene network during organogenesis due to the repeated interaction of Abd-B and one of its targets, the JAK/STAT signalling cascade. Our results show that in this network STAT functions not just as a direct transcription factor, but also acts as a "counter-repressor", uncovering a novel mode for STAT directed transcriptional regulation.
authors.affiliation: Centro Andaluz de Biología de Desarrollo, CSIC/JA, Universidad Pablo de Olivde, Seville, Spain.
authors.forename: Pedro B
authors.initials: PB
authors.lastname: Pinto
authors.affiliation: Centro Andaluz de Biología de Desarrollo, CSIC/JA, Universidad Pablo de Olivde, Seville, Spain.
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Espinosa-Vázquez
authors.affiliation: Centro Andaluz de Biología de Desarrollo, CSIC/JA, Universidad Pablo de Olivde, Seville, Spain.
authors.forename: María Luísa
authors.initials: ML
authors.lastname: Rivas
authors.affiliation: Centro Andaluz de Biología de Desarrollo, CSIC/JA, Universidad Pablo de Olivde, Seville, Spain.
authors.forename: James Castelli-Gair
authors.initials: JC
authors.lastname: Hombría
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks / Q000235:genetics*; D005801:Genes, Homeobox / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D053612:Janus Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D038081:Organogenesis / Q000235:genetics*; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: C062393:Abd-B proteins, Drosophila; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D050791:STAT Transcription Factors; C105675:Stat92E protein, Drosophila; C064360:crb protein, Drosophila; D053612:Janus Kinases