JAK/STAT and Hox Dynamic Interactions in an Organogenetic Gene Cascade.
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 or...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-07-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC4521708?pdf=render |
| _version_ | 1818158765821657088 |
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| author | Pedro B Pinto Jose Manuel Espinosa-Vázquez María Luísa Rivas James Castelli-Gair Hombría |
| author_facet | Pedro B Pinto Jose Manuel Espinosa-Vázquez María Luísa Rivas James Castelli-Gair Hombría |
| author_sort | Pedro B Pinto |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T15:35:18Z |
| format | Article |
| id | doaj.art-2f8799e0b8784d78a1ae95f4fdccabf3 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-11T15:35:18Z |
| publishDate | 2015-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-2f8799e0b8784d78a1ae95f4fdccabf32022-12-22T00:59:57ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042015-07-01117e100541210.1371/journal.pgen.1005412JAK/STAT and Hox Dynamic Interactions in an Organogenetic Gene Cascade.Pedro B PintoJose Manuel Espinosa-VázquezMaría Luísa RivasJames Castelli-Gair HombríaOrganogenesis 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.http://europepmc.org/articles/PMC4521708?pdf=render |
| spellingShingle | Pedro B Pinto Jose Manuel Espinosa-Vázquez María Luísa Rivas James Castelli-Gair Hombría JAK/STAT and Hox Dynamic Interactions in an Organogenetic Gene Cascade. PLoS Genetics |
| title | JAK/STAT and Hox Dynamic Interactions in an Organogenetic Gene Cascade. |
| title_full | JAK/STAT and Hox Dynamic Interactions in an Organogenetic Gene Cascade. |
| title_fullStr | JAK/STAT and Hox Dynamic Interactions in an Organogenetic Gene Cascade. |
| title_full_unstemmed | JAK/STAT and Hox Dynamic Interactions in an Organogenetic Gene Cascade. |
| title_short | JAK/STAT and Hox Dynamic Interactions in an Organogenetic Gene Cascade. |
| title_sort | jak stat and hox dynamic interactions in an organogenetic gene cascade |
| url | http://europepmc.org/articles/PMC4521708?pdf=render |
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