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Title

JAK/STAT and Hox dynamic interactions in an organogenetic gene cascade

AuthorsPinto, Pedro ; Espinosa-Vázquez, José Manuel; Rivas, María Luisa ; Castelli-Gair Hombría, James
Issue Date2015
PublisherPublic Library of Science
CitationPLoS Genetics 11(7): e1005412 (2015)
AbstractOrganogenesis 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.
DescriptionThis is an open access article distributed under the terms of the Creative Commons Attribution License.
Publisher version (URL)http://dx.doi.org/10.1371/journal.pgen.1005412
URIhttp://hdl.handle.net/10261/129579
DOI10.1371/journal.pgen.1005412
Identifiersdoi: 10.1371/journal.pgen.1005412
e-issn: 1553-7404
issn: 1553-7390
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