Extraembryonic mesoderm in primate and rodent embryos and models

Abstract

Extraembryonic mesenchymal cells/mesoderm cells (Exmes/EXMC) are mesenchymal-like populations located outside the embryo proper during early amniote development. They line the amnion and yolk sac, form the placental villous core, and build the connecting stalk. They are essential for extraembryonic tissue support, early hematopoiesis and vascular development. Yet their developmental origins and lineage relationships remain partially resolved, particularly across species. In rodents, EXMC arise during gastrulation from newly specified mesoderm emerging from the primitive streak. In primates including humans, by contrast, extraembryonic mesenchymal cells (Exmes) are detectable in the post-implantation but pre-gastrulation conceptus, before the formation of gastrulation-derived mesoderm. Here, focusing on the peri-implantation to early-organogenesis time window (CS3-CS9 in primates; E4.5-E8.5 in rodents), we review histological, genetic, and single-cell multi-omic evidence on the emergence, diversification, and functional specialization of pre-gastrulation Exmes/post-gastrulation EXMC, with particular attention to their roles in yolk sac and placental hematopoiesis, vascularization, and tissue homeostasis. We further discuss insights from non-human primate models and human stem cell-based embryo models that generate Exmes/EXMC-like populations in vitro. Finally, we outline key challenges for resolving the origins of these cells, defining conserved and species-specific regulatory programs, and leveraging Exmes/EXMC biology to understand pregnancy loss, placental disorders, early hematopoietic and vascular development.

Keywords

Exmes/EXMC / hematopoiesis / vascularization / embryo models

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