Prummel, Karin DKarin DPrummelCrowell, Helena LHelena LCrowellNieuwenhuize, SusanSusanNieuwenhuizeBrombacher, Eline CEline CBrombacherDaetwyler, StephanStephanDaetwylerSoneson, CharlotteCharlotteSonesonKresoja-Rakic, JelenaJelenaKresoja-RakicKocere, AgneseAgneseKocereRonner, ManuelManuelRonnerErnst, Alexander Uwe JohannAlexander Uwe JohannErnst0000-0002-4956-315XLabbaf, ZahraZahraLabbafClouthier, David EDavid EClouthierFirulli, Anthony BAnthony BFirulliSánchez-Iranzo, HéctorHéctorSánchez-IranzoNaganathan, Sundar RSundar RNaganathanO'Rourke, RebeccaRebeccaO'RourkeRaz, ErezErezRazMercader Huber, Nadia IsabelNadia IsabelMercader Huber0000-0002-0905-6399Burger, AlexaAlexaBurgerFelley-Bosco, EmanuelaEmanuelaFelley-BoscoHuisken, JanJanHuiskenRobinson, Mark DMark DRobinsonMosimann, ChristianChristianMosimann2024-10-092024-10-092022-03-30https://boris-portal.unibe.ch/handle/20.500.12422/69840The mesothelium lines body cavities and surrounds internal organs, widely contributing to homeostasis and regeneration. Mesothelium disruptions cause visceral anomalies and mesothelioma tumors. Nonetheless, the embryonic emergence of mesothelia remains incompletely understood. Here, we track mesothelial origins in the lateral plate mesoderm (LPM) using zebrafish. Single-cell transcriptomics uncovers a post-gastrulation gene expression signature centered on hand2 in distinct LPM progenitor cells. We map mesothelial progenitors to lateral-most, hand2-expressing LPM and confirm conservation in mouse. Time-lapse imaging of zebrafish hand2 reporter embryos captures mesothelium formation including pericardium, visceral, and parietal peritoneum. We find primordial germ cells migrate with the forming mesothelium as ventral migration boundary. Functionally, hand2 loss disrupts mesothelium formation with reduced progenitor cells and perturbed migration. In mouse and human mesothelioma, we document expression of LPM-associated transcription factors including Hand2, suggesting re-initiation of a developmental program. Our data connects mesothelium development to Hand2, expanding our understanding of mesothelial pathologies.en600 - Technology::610 - Medicine & healtharticle10.48350/1688573535481710.1038/s41467-022-29311-7