A conserved regulatory program initiates lateral plate mesoderm emergence across chordates
- Creators
- Prummel, Karin D.
- Hess, Christopher
- Nieuwenhuize, Susan
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Parker, Hugo J.
- Rogers, Katherine W.
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Kozmikova, Iryna
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Racioppi, Claudia
- Brombacher, Eline C.
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Czarkwiani, Anna
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Knapp, Dunja
- Burger, Sibylle
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Chiavacci, Elena
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Shah, Gopi
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Burger, Alexa
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Huisken, Jan
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Yun, Maximina H.
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Christiaen, Lionel
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Kozmik, Zbynek
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Müller, Patrick
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Bronner, Marianne
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Krumlauf, Robb
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Mosimann, Christian
Abstract
Cardiovascular lineages develop together with kidney, smooth muscle, and limb connective tissue progenitors from the lateral plate mesoderm (LPM). How the LPM initially emerges and how its downstream fates are molecularly interconnected remain unknown. Here, we isolate a pan-LPM enhancer in the zebrafish-specific draculin (drl) gene that provides specific LPM reporter activity from early gastrulation. In toto live imaging and lineage tracing of drl-based reporters captures the dynamic LPM emergence as lineage-restricted mesendoderm field. The drl pan-LPM enhancer responds to the transcription factors EomesoderminA, FoxH1, and MixL1 that combined with Smad activity drive LPM emergence. We uncover specific activity of zebrafish-derived drl reporters in LPM-corresponding territories of several chordates including chicken, axolotl, lamprey, Ciona, and amphioxus, revealing a universal upstream LPM program. Altogether, our work provides a mechanistic framework for LPM emergence as defined progenitor field, possibly representing an ancient mesodermal cell state that predates the primordial vertebrate embryo.
Additional Information
© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received: 8 April 2019. Accepted: 22 July 2019. Published online: 26 August 2019. We thank Seraina Bötschi, Lukas Obernosterer, and Vesna Barros for technical and husbandry support; the lab of Stephan Neuhauss for zebrafish husbandry support; the labs of Esther Stöckli and Jerome Gros for chicken experimentation support; the ZMB at UZH for imaging support; Fiona Wardle for input and support on the ChIP-seq panel in Fig. 5a; the lab of Magdalini Polymenidou for vibratome access; Karolína Ditrychová for cloning the pKD001 construct; Rebecca Burdine for sharing transcription factor constructs; Mark Miller for animal illustrations in Fig. 7a; the Stowers Institute histology facility for assistance with lamprey embryo sectioning; Hans-Henning Epperlein for discussions on salamander embryology; Diego Safian for suggesting Genomicus for synteny analysis; and all members of the Mosimann lab for constructive input. This work has been supported by a Swiss National Science Foundation (SNSF) professorship [PP00P3_139093] and SNSF R'Equip grant 150838 (Lightsheet Fluorescence Microscopy), a Marie Curie Career Integration Grant from the European Commission [CIG PCIG14-GA-2013-631984], the Canton of Zürich, the UZH Foundation for Research in Science and the Humanities, the Swiss Heart Foundation, and the ZUNIV FAN/UZH Alumni to C.M.; a UZH CanDoc to C.H.; EuFishBioMed and Company of Biologists travel fellowships to K.D.P.; the Stowers Institute (grant #1001) to H.J.P. and R.K.; NIH/NHLBI R01 award HL108643, trans-Atlantic network of excellence award 15CVD01 from the Leducq Foundation to L.C.; a long-term fellowship ALTF 1608-2014 from EMBO to C.R.; Alexander von Humboldt fellowship to A.C. and DFG Research Center (DFG FZ 111) and Cluster of Excellence (DFG EXC 168) funds to M.H.Y.; Czech Science Foundation 17-15374 S to Z.K. Data availability: The authors declare that the data supporting the findings of this study are available within the paper and its supplementary information files. Original data underlying the lamprey experiments in this manuscript are accessible from the Stowers Original Data Repository at http://odr.stowers.org/websimr/. The source data underlying Fig. 2j and Supplementary Fig. 2b and 10m are provided as a Source Data file. Reagents are available upon request. These authors contributed equally: Karin D. Prummel, Christopher Hess. Author Contributions: K.D.P., C.H., S.N., E.C.B., S.B., and C.M. designed, performed, and interpreted the zebrafish experiments; S.N., E.C., and A.B. established and performed the chicken experiments; K.D.P. performed the lightsheet imaging with technical and equipment support by G.S. and J.H.; K.W.R. and P.M. provided and generated mutants and maternal-zygotic mutant zebrafish; H.J.P., M.B., and R.K. designed, performed, and interpreted the lamprey experiments; A.C., D.K., and M.H.Y. designed, performed, and interpreted the axolotl experiments; C.R. and L.C. designed, performed, and interpreted the Ciona experiments; I.K. and Z.K. designed, performed, and interpreted the amphioxus experiments; A.C., D.K., and M.H.Y. designed and performed the axolotl experiments; K.D.P., C.H., S.N., and C.M. assembled and wrote the manuscript with contributions from all co-authors. The authors declare no competing interests. Nature Communications thanks the anonymous reviewers for their contribution to the peer review of this work. Peer reviewer reports are available.Attached Files
Published - s41467-019-11561-7.pdf
Supplemental Material - 41467_2019_11561_MOESM1_ESM.pdf
Supplemental Material - 41467_2019_11561_MOESM2_ESM.mp4
Supplemental Material - 41467_2019_11561_MOESM3_ESM.mp4
Supplemental Material - 41467_2019_11561_MOESM4_ESM.mp4
Supplemental Material - 41467_2019_11561_MOESM5_ESM.mp4
Supplemental Material - 41467_2019_11561_MOESM6_ESM.pdf
Supplemental Material - 41467_2019_11561_MOESM7_ESM.pdf
Supplemental Material - 41467_2019_11561_MOESM8_ESM.pdf
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Additional details
- PMCID
- PMC6710290
- Eprint ID
- 98397
- Resolver ID
- CaltechAUTHORS:20190903-130241403
- PP00P3_139093
- Swiss National Science Foundation (SNSF)
- 150838
- Swiss National Science Foundation (SNSF)
- CIG PCIG14-GA-2013-631984
- Marie Curie Fellowship
- Canton of Zürich
- UZH Foundation for Research in Science and the Humanities
- Swiss Heart Foundation
- ZUNIV FAN/UZH Alumni
- Universität Zürich
- EuFishBioMed
- Company of Biologists
- 1001
- Stowers Institute
- HL108643
- NIH
- 15CVD01
- Leducq Foundation
- ALTF 1608-2014
- European Molecular Biology Organization (EMBO)
- Alexander von Humboldt Foundation
- DFG FZ 111
- Deutsche Forschungsgemeinschaft (DFG)
- DFG EXC 168
- Deutsche Forschungsgemeinschaft (DFG)
- 17-15374
- Czech Science Foundation
- Created
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2019-09-03Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field