A conserved regulatory program drives emergence of the lateral plate mesoderm

Author:

Prummel Karin D.,Hess Christopher,Nieuwenhuize Susan,Parker Hugo J.,Rogers Katherine W.,Kozmikova IrynaORCID,Racioppi ClaudiaORCID,Brombacher Eline C.,Czarkwiani Anna,Knapp Dunja,Burger SibylleORCID,Chiavacci Elena,Shah Gopi,Burger Alexa,Huisken JanORCID,Yun Maximina H.,Christiaen LionelORCID,Kozmik ZbynekORCID,Müller Patrick,Bronner MarianneORCID,Krumlauf RobbORCID,Mosimann ChristianORCID

Abstract

AbstractCardiovascular 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 isolated a pan-LPM enhancer in the zebrafish draculin (drl) gene that provides specific LPM reporter activity from early gastrulation. In toto live imaging and lineage tracing of drl-based reporters captured 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 uncovered specific drl reporter activity 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.

Publisher

Cold Spring Harbor Laboratory

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