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A conserved regulatory program drives emergence of the lateral plate mesoderm

Hess, Christopher and Prummel, Karin D. and Nieuwenhuize, Susan and Parker, Hugo J. and Rogers, Katherine W. and Kozmikova, Iryna and Racioppi, Claudia and Burger, Sibylle and Brombacher, Eline C. and Burger, Alexa and Felker, Anastasia and Chiavacci, Elena and Shah, Gopi and Huisken, Jan and Kozmik, Zbynek and Christiaen, Lionel and Müller, Patrick and Bronner, Marianne and Krumlauf, Robb and Mosimann, Christian (2018) A conserved regulatory program drives emergence of the lateral plate mesoderm. . (Unpublished)

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Cardiovascular cell lineages emerge with kidney, smooth muscle, and limb skeleton progenitors from the lateral plate mesoderm (LPM). How the LPM emerges during development and how it has evolved to form key lineages of the vertebrate body plan remain unknown. Here, we captured LPM formation by transgenic in toto imaging and lineage tracing using the first pan-LPM enhancer element from the zebrafish gene draculin (drl). drl LPM enhancer-based reporters are specifically active in LPM-corresponding territories of several chordate species, uncovering a universal LPM-specific gene program. Distinct from other mesoderm, we identified EomesA, FoxH1, and MixL1 with BMP/Nodal-controlled Smad activity as minimally required factors to drive drl-marked LPM formation. Altogether, our work provides a developmental and mechanistic framework for LPM emergence and the in vitro differentiation of cardiovascular cell types. Our findings suggest that the LPM may represent an ancient cell fate domain that predates ancestral vertebrates.

Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription Paper
Parker, Hugo J.0000-0001-7646-2007
Kozmikova, Iryna0000-0002-7861-9802
Racioppi, Claudia0000-0001-8117-1124
Burger, Alexa0000-0001-7137-3910
Chiavacci, Elena0000-0003-3924-3635
Huisken, Jan0000-0001-7250-3756
Kozmik, Zbynek0000-0002-5850-2105
Christiaen, Lionel0000-0001-5930-5667
Müller, Patrick0000-0002-0702-6209
Bronner, Marianne0000-0003-4274-1862
Krumlauf, Robb0000-0001-9102-7927
Mosimann, Christian0000-0002-0749-2576
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. bioRxiv preprint first posted online Feb. 7, 2018. Author Contributions: C.H, K.D.P., S.N., S.B, C.M. designed, performed, and interpreted zebrafish experiments; S.N., E.C., A.B. performed chicken experiments; K. P. performed lightsheet imaging with technical and equipment support by G.S., J.H; E.C.B, K.P., A.F. performed section-based zebrafish lineage tracing; K.W.R, P.M. provided and generated mutants and maternal-zygotic mutant zebrafish; H.J.P, M.B., R.K. designed, performed, and interpreted lamprey experiments; C.R., L.C. designed, performed, and interpreted Ciona experiments; I.K, Z.K designed, performed, and interpreted amphioxus experiments; C.H., K.P., and C.M. assembled and wrote the manuscript with contributions from all co-authors. We thank Sibylle Burger and Seraina Bötschi for technical and husbandry support; the lab of Dr. Stephan Neuhauss for zebrafish husbandry support; the labs of Dr. Esther Stöckli and Dr. Jerome Gros for chicken experimentation support; the ZBM at UZH for imaging support; Dr. Fiona Wardle for input and support on the ChIP-seq panel in Fig. 4E; the lab of Dr. Magdalini Polymenidou for vibratome access; Karolína Ditrychová for cloning the pKD001 construct; Dr. Ashley Bruce, Dr. Rebecca Burdine, and Dr. Michael Tsang for sharing transcription factor constructs; the Stowers Institute histology facility for assistance with lamprey embryo sectioning; 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.
Funding AgencyGrant Number
Swiss National Science Foundation (SNSF)PP00P3_139093
Swiss National Science Foundation (SNSF)150838
Marie Curie FellowshipCIG PCIG14-GA-2013-631984
Canton of ZürichUNSPECIFIED
Swiss Heart FoundationUNSPECIFIED
University of ZürichUNSPECIFIED
Company of BiologistsUNSPECIFIED
Stowers Institute1001
Leducq Foundation15CVD01
European Molecular Biology Organization (EMBO)1608-2014
Record Number:CaltechAUTHORS:20181031-083913600
Persistent URL:
Official Citation:A conserved regulatory program drives emergence of the lateral plate mesoderm. Christopher Hess, Karin Dorien Prummel, Susan Nieuwenhuize, Hugo Parker, Katherine W. Rogers, Iryna Kozmikova, Claudia Racioppi, Sibylle Burger, Eline C. Brombacher, Alexa Burger, Anastasia Felker, Elena Chiavacci, Gopi Shah, Jan Huisken, Zbynek Kozmik, Lionel Christiaen, Patrick Mueller, Marianne Bronner, Robb Krumlauf, Christian Mosimann. bioRxiv 261115; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:90534
Deposited By: Tony Diaz
Deposited On:01 Nov 2018 18:21
Last Modified:16 Nov 2021 03:33

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