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Nat Commun. 2019 Aug 26;10(1):3857. doi: 10.1038/s41467-019-11561-7.

A conserved regulatory program initiates lateral plate mesoderm emergence across chordates.

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Institute of Molecular Life Sciences, University of Zurich, Zürich, 8057, Switzerland.
Department of Anatomy and Cell Biology, Kansas University Medical Center, Kansas City, KS, 66160, USA.
Stowers Institute for Medical Research, Kansas City, MO, 64110, USA.
Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, 72076, Germany.
Institute of Molecular Genetics of the ASCR, Prague, 142 20, Czech Republic.
Center for Developmental Genetics, Department of Biology, New York University, New York, NY, 10003, USA.
TUD-CRTD Center for Regenerative Therapies Dresden, Dresden, 01307, Germany.
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, 01307, Germany.
Morgridge Institute for Research, Madison, WI, 53715, USA.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Institute of Molecular Life Sciences, University of Zurich, Zürich, 8057, Switzerland.


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.

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