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BMP signalling regulates the pre-implantation development of extra-embryonic cell lineages in the mouse embryo

Graham, Sarah J. L. and Wicher, Krzysztof B. and Jedrusik, Agnieszka and Guo, Guoji and Herath, Wishva and Robson, Paul and Zernicka-Goetz, Magdalena (2014) BMP signalling regulates the pre-implantation development of extra-embryonic cell lineages in the mouse embryo. Nature Communications, 5 . Art. No. 5667. ISSN 2041-1723. PMCID PMC4338527. doi:10.1038/ncomms6667.

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Pre-implantation development requires the specification and organization of embryonic and extra-embryonic lineages. The separation of these lineages takes place when asymmetric divisions generate inside and outside cells that differ in polarity, position and fate. Here we assess the global transcriptional identities of these precursor cells to gain insight into the molecular mechanisms regulating lineage segregation. Unexpectedly, this reveals that complementary components of the bone morphogenetic protein (BMP) signalling pathway are already differentially expressed after the first wave of asymmetric divisions. We investigate the role of BMP signalling by expressing dominant negative forms of Smad4 and Bmpr2, by downregulating the pathway using RNA interference against BMP ligands and by applying three different BMP inhibitors at distinct stages. This reveals that BMP signalling regulates the correct development of both extra-embryonic lineages, primitive endoderm and trophectoderm, but not the embryonic lineage, before implantation. Together, these findings indicate multiple roles of BMP signalling in the early mouse embryo.

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Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2014 Nature Publishing Group. Received 30 May 2014. Accepted 24 October 2014. Published 16 December 2014. We are grateful to Ivan Bedzhov for the pSmad1 staining and the members of our group and David Glover for helpful discussions. This work was supported by a Wellcome Trust programme grant to M.Z.-G. and an Agency for Science, Technology and Research (A*Star) core research budget to P.R. Author Contributions: S.J.L.G. designed and performed experiments, analysed data and wrote the manuscript. K.B.W. analysed the sequencing data and contributed to experiments. A.J. isolated the cells for mRNA sequencing. G.G., W.H. and P.R. performed the deep sequencing and initial data analysis. M.Z.-G. designed the experiments and helped to interpret the results and write the manuscript. Accession codes: NCBI BioSample accession numbers are SAMN03098868 (outside cells) and SAMN03098869 (inside cells). Sequencing data have been deposited in the NCBI short read archive under BioProject ID PRJNA263313. The authors declare no competing financial interests.
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Agency for Science, Technology and Research (A*STAR)UNSPECIFIED
PubMed Central ID:PMC4338527
Record Number:CaltechAUTHORS:20190405-170316127
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Official Citation:S. J. L. et al. BMP signalling regulates the pre-implantation development of extra-embryonic cell lineages in the mouse embryo. Nat. Commun. 5:5667 doi: 10.1038/ncomms6667 (2014).
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94547
Deposited By: George Porter
Deposited On:09 Apr 2019 22:58
Last Modified:16 Nov 2021 17:05

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