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...

Full description

Saved in:
Bibliographic Details
Main Authors: Lisa Deignan, Marco T Pinheiro, Catherine Sutcliffe, Abbie Saunders, Scott G Wilcockson, Leo A H Zeef, Ian J Donaldson, Hilary L Ashe
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-07-01
Series:PLoS Genetics
Online Access:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006164&type=printable
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849472598243540992
author Lisa Deignan
Marco T Pinheiro
Catherine Sutcliffe
Abbie Saunders
Scott G Wilcockson
Leo A H Zeef
Ian J Donaldson
Hilary L Ashe
author_facet Lisa Deignan
Marco T Pinheiro
Catherine Sutcliffe
Abbie Saunders
Scott G Wilcockson
Leo A H Zeef
Ian J Donaldson
Hilary L Ashe
author_sort Lisa Deignan
collection DOAJ
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.
format Article
id doaj-art-bed30bb8962a4b00b74ed4bb17fea2df
institution Kabale University
issn 1553-7390
1553-7404
language English
publishDate 2016-07-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS Genetics
spelling doaj-art-bed30bb8962a4b00b74ed4bb17fea2df2025-08-20T03:24:29ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042016-07-01127e100616410.1371/journal.pgen.1006164Regulation of the BMP Signaling-Responsive Transcriptional Network in the Drosophila Embryo.Lisa DeignanMarco T PinheiroCatherine SutcliffeAbbie SaundersScott G WilcocksonLeo A H ZeefIan J DonaldsonHilary L AsheThe 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.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006164&type=printable
spellingShingle Lisa Deignan
Marco T Pinheiro
Catherine Sutcliffe
Abbie Saunders
Scott G Wilcockson
Leo A H Zeef
Ian J Donaldson
Hilary L Ashe
Regulation of the BMP Signaling-Responsive Transcriptional Network in the Drosophila Embryo.
PLoS Genetics
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
url https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006164&type=printable
work_keys_str_mv AT lisadeignan regulationofthebmpsignalingresponsivetranscriptionalnetworkinthedrosophilaembryo
AT marcotpinheiro regulationofthebmpsignalingresponsivetranscriptionalnetworkinthedrosophilaembryo
AT catherinesutcliffe regulationofthebmpsignalingresponsivetranscriptionalnetworkinthedrosophilaembryo
AT abbiesaunders regulationofthebmpsignalingresponsivetranscriptionalnetworkinthedrosophilaembryo
AT scottgwilcockson regulationofthebmpsignalingresponsivetranscriptionalnetworkinthedrosophilaembryo
AT leoahzeef regulationofthebmpsignalingresponsivetranscriptionalnetworkinthedrosophilaembryo
AT ianjdonaldson regulationofthebmpsignalingresponsivetranscriptionalnetworkinthedrosophilaembryo
AT hilarylashe regulationofthebmpsignalingresponsivetranscriptionalnetworkinthedrosophilaembryo