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Regulation of the BMP Signaling-Responsive Transcriptional Network in the Drosophila Embryo

The BMP signaling pathway has a conserved role in dorsal-ventral axis patterning during embryonic development. In Drosophila, graded BMP signaling is transduced by the Mad transcription factor and opposed by the Brinker repressor. In this study, using the Drosophila embryo as a model, we combine RNA...

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Autores principales: Deignan, Lisa, Pinheiro, Marco T., Sutcliffe, Catherine, Saunders, Abbie, Wilcockson, Scott G., Zeef, Leo A. H., Donaldson, Ian J., Ashe, Hilary L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933369/
https://www.ncbi.nlm.nih.gov/pubmed/27379389
http://dx.doi.org/10.1371/journal.pgen.1006164
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author Deignan, Lisa
Pinheiro, Marco T.
Sutcliffe, Catherine
Saunders, Abbie
Wilcockson, Scott G.
Zeef, Leo A. H.
Donaldson, Ian J.
Ashe, Hilary L.
author_facet Deignan, Lisa
Pinheiro, Marco T.
Sutcliffe, Catherine
Saunders, Abbie
Wilcockson, Scott G.
Zeef, Leo A. H.
Donaldson, Ian J.
Ashe, Hilary L.
author_sort Deignan, Lisa
collection PubMed
description The BMP signaling pathway has a conserved role in dorsal-ventral axis patterning during embryonic development. In Drosophila, graded BMP signaling is transduced by the Mad transcription factor and opposed by the Brinker repressor. In this study, using the Drosophila embryo as a model, we combine RNA-seq with Mad and Brinker ChIP-seq to decipher the BMP-responsive transcriptional network underpinning differentiation of the dorsal ectoderm during dorsal-ventral axis patterning. We identify multiple new BMP target genes, including positive and negative regulators of EGF signaling. Manipulation of EGF signaling levels by loss- and gain-of-function studies reveals that EGF signaling negatively regulates embryonic BMP-responsive transcription. Therefore, the BMP gene network has a self-regulating property in that it establishes a balance between its activity and that of the antagonistic EGF signaling pathway to facilitate correct patterning. In terms of BMP-dependent transcription, we identify key roles for the Zelda and Zerknüllt transcription factors in establishing the resulting expression domain, and find widespread binding of insulator proteins to the Mad and Brinker-bound genomic regions. Analysis of embryos lacking the BEAF-32 insulator protein shows reduced transcription of a peak BMP target gene and a reduction in the number of amnioserosa cells, the fate specified by peak BMP signaling. We incorporate our findings into a model for Mad-dependent activation, and discuss its relevance to BMP signal interpretation in vertebrates.
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spelling pubmed-49333692016-07-18 Regulation of the BMP Signaling-Responsive Transcriptional Network in the Drosophila Embryo Deignan, Lisa Pinheiro, Marco T. Sutcliffe, Catherine Saunders, Abbie Wilcockson, Scott G. Zeef, Leo A. H. Donaldson, Ian J. Ashe, Hilary L. PLoS Genet Research Article The BMP signaling pathway has a conserved role in dorsal-ventral axis patterning during embryonic development. In Drosophila, graded BMP signaling is transduced by the Mad transcription factor and opposed by the Brinker repressor. In this study, using the Drosophila embryo as a model, we combine RNA-seq with Mad and Brinker ChIP-seq to decipher the BMP-responsive transcriptional network underpinning differentiation of the dorsal ectoderm during dorsal-ventral axis patterning. We identify multiple new BMP target genes, including positive and negative regulators of EGF signaling. Manipulation of EGF signaling levels by loss- and gain-of-function studies reveals that EGF signaling negatively regulates embryonic BMP-responsive transcription. Therefore, the BMP gene network has a self-regulating property in that it establishes a balance between its activity and that of the antagonistic EGF signaling pathway to facilitate correct patterning. In terms of BMP-dependent transcription, we identify key roles for the Zelda and Zerknüllt transcription factors in establishing the resulting expression domain, and find widespread binding of insulator proteins to the Mad and Brinker-bound genomic regions. Analysis of embryos lacking the BEAF-32 insulator protein shows reduced transcription of a peak BMP target gene and a reduction in the number of amnioserosa cells, the fate specified by peak BMP signaling. We incorporate our findings into a model for Mad-dependent activation, and discuss its relevance to BMP signal interpretation in vertebrates. Public Library of Science 2016-07-05 /pmc/articles/PMC4933369/ /pubmed/27379389 http://dx.doi.org/10.1371/journal.pgen.1006164 Text en © 2016 Deignan et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Deignan, Lisa
Pinheiro, Marco T.
Sutcliffe, Catherine
Saunders, Abbie
Wilcockson, Scott G.
Zeef, Leo A. H.
Donaldson, Ian J.
Ashe, Hilary L.
Regulation of the BMP Signaling-Responsive Transcriptional Network in the Drosophila Embryo
title Regulation of the BMP Signaling-Responsive Transcriptional Network in the Drosophila Embryo
title_full Regulation of the BMP Signaling-Responsive Transcriptional Network in the Drosophila Embryo
title_fullStr Regulation of the BMP Signaling-Responsive Transcriptional Network in the Drosophila Embryo
title_full_unstemmed Regulation of the BMP Signaling-Responsive Transcriptional Network in the Drosophila Embryo
title_short Regulation of the BMP Signaling-Responsive Transcriptional Network in the Drosophila Embryo
title_sort regulation of the bmp signaling-responsive transcriptional network in the drosophila embryo
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933369/
https://www.ncbi.nlm.nih.gov/pubmed/27379389
http://dx.doi.org/10.1371/journal.pgen.1006164
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