Extra-embryonic tissues provide protection and nutrition in vertebrates, as well as a connection to the maternal tissues in mammals. The extra-embryonic mesoderm is an essential and understudied germ layer present in amniotes. It is involved in hematopoiesis, as well as in the formation of extra-embryonic structures such as the amnion, umbilical cord and placenta. The origin and specification of extra-embryonic mesoderm are not entirely conserved across species, and the molecular mechanisms governing its formation and function are not fully understood. This Review begins with an overview of the embryonic origin and function of extra-embryonic mesoderm in vertebrates from in vivo studies. We then compare in vitro models that generate extra-embryonic mesoderm-like cells. Finally, we discuss how insights from studying both embryos and in vitro systems can aid in designing even more advanced stem cell-based embryo models.

Funding

E.N. received a Formation à la Recherche dans l'Industrie et l'Agriculture (FRIA) fellowship from the Fonds De La Recherche Scientifique – FNRS. I.M. is a senior FNRS research associate. Research in the Pasque laboratory is supported by Fonds Wetenschappelijk Onderzoek (FWO; Odysseus Return Grant G0F7716N to V.P.; FWO grants G0C9320N and G0B4420N to V.P.), the Onderzoeksraad, KU Leuven Research Fund (C1 grants C14/21/19 to V.P. and project financing) and Pandarome project 40007487 (G0I7822N; funded by the FWO and FNRS) under the Excellence of Science (EOS) program (to V.P.).

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