Human embryonic development: from peri-implantation to gastrulation

Abstract

In vitro culture of mammalian embryos, especially primate embryos, greatly enriches our knowledge of the dynamic characteristics of human early embryo development.Culturing non-human primate embryos beyond the gastrulation stage is one of the best strategies to understand human gastrulation.Reconstructions of stem cell–based embryo models provide insight to decipher the mechanisms underlying human embryogenesis.Advancements in single-cell multiomic studies and imaging techniques contribute to clarifying the cell lineage trajectory and unveiling the underpinning molecular mechanisms of human embryogenesis and gastrulation. The basic body plan of the mammalian embryo is established through gastrulation, a pivotal early postimplantation event during which the three major germ layers (endoderm, ectoderm, and mesoderm) are specified with cellular and spatial diversity. Despite its basic and clinical importance, human embryo development from peri-implantation to gastrulation remains shrouded in mystery. Recent advances in the elongated in vitro culture of rodent and non‐primate embryos and the construction of embryo-like structures have helped to improve understanding of the mechanisms of human early embryonic development. Here, we review the recent advances and possible future directions in the development of in vitro models to better understand human embryogenesis from peri-implantation to gastrulation. The basic body plan of the mammalian embryo is established through gastrulation, a pivotal early postimplantation event during which the three major germ layers (endoderm, ectoderm, and mesoderm) are specified with cellular and spatial diversity. Despite its basic and clinical importance, human embryo development from peri-implantation to gastrulation remains shrouded in mystery. Recent advances in the elongated in vitro culture of rodent and non‐primate embryos and the construction of embryo-like structures have helped to improve understanding of the mechanisms of human early embryonic development. Here, we review the recent advances and possible future directions in the development of in vitro models to better understand human embryogenesis from peri-implantation to gastrulation. Early human embryonic development from peri-implantation to gastrulation has always been a very active yet difficult field of developmental biology (Box 1 and Figure 1A ). Errors in this process may lead to adverse pregnancy outcomes, including miscarriage and fetal defects. Understanding the mechanisms underlying early human development is of great importance not only for basic developmental biology but also for regenerative medicine. However, scientists have been puzzling over this Pandora’s box because the embryos are hardly accessible. Most of our knowledge about human embryogenesis from peri-implantation to gastrulation is derived from studies on existing anatomical and histological collections of natural human embryos. Lessons from mouse models also enrich our understanding of human embryonic development from a mammalian point of view (Figure 1A,B).Box 1Major events of human early embryonic development from peri-implantation to gastrulationHuman embryonic development starts with the formation of the totipotent zygotes during fertilization. The zygotes develop into a blastula through several rounds of cleavage division, and the blastula hatches from the zona pellucida and attaches to the maternal endometrium for embryo implantation at approximately E6–E7 (CS4). At approximately E7–E9 (CS5a), the epiblast gradually exits from its pluripotent state and changes into a group of radially oriented cells surrounding a small primordial cavity, the proamniotic cavity. Primitive endoderm (PE) cells grow underneath the trophectoderm (TE) to form parietal PE (parPE) and arrange beneath the ventral side of the epiblast to construct the ventral endoderm (VE). At E10–E11 (CS5b), with the formation of the amniotic cavity (AC) through proamniotic cavity expansion, epiblast cells on the dorsal part of the proamniotic cavity form a layer of squamous amnion epithelium [43.Deglincerti A. et al.Self-organization of the in vitro attached human embryo.Nature. 2016; 533: 251-254Crossref PubMed Scopus (337) Google Scholar,44.Shahbazi M.N. et al.Self-organization of the human embryo in the absence of maternal tissues.Nat. Cell Biol. 2016; 18: 700-708Crossref PubMed Scopus (325) Google Scholar], whereas the cells on the ventral part keep their goblet morphology and develop into late epiblasts [6.Xiang L. et al.A developmental of human PubMed Scopus Google At the cells form the with PE At the epiblast into The to form the which also of a on the ventral part of the this embryonic is the Figure 1A in At the human embryo the gastrulation is a event in early embryonic development because the for three germ layers and the body embryo at the gastrulation stage with three germ layers is a embryonic gastrulation with the of the at the of epiblasts on the of cells and The the of the body and a for the of epiblast the of and the of epiblasts the Figure 1A in The major of human and late gastrulation have been et The embryo and its Biol. PubMed Scopus Google et development of the human PubMed Scopus Google the biology of human embryo development from peri-implantation to gastrulation is from developmental events and molecular of mouse embryos at stage Figure in have been embryonic development starts with the formation of the totipotent zygotes during fertilization. The zygotes develop into a blastula through several rounds of cleavage division, and the blastula hatches from the zona pellucida and attaches to the maternal endometrium for embryo implantation at approximately E6–E7 (CS4). At approximately E7–E9 (CS5a), the epiblast gradually exits from its pluripotent state and changes into a group of radially oriented cells surrounding a small primordial cavity, the proamniotic cavity. Primitive endoderm (PE) cells grow underneath the trophectoderm (TE) to form parietal PE (parPE) and arrange beneath the ventral side of the epiblast to construct the ventral endoderm (VE). At E10–E11 (CS5b), with the formation of the amniotic cavity (AC) through proamniotic cavity expansion, epiblast cells on the dorsal part of the proamniotic cavity form a layer of squamous amnion epithelium [43.Deglincerti A. et al.Self-organization of the in vitro attached human embryo.Nature. 2016; 533: 251-254Crossref PubMed Scopus (337) Google Scholar,44.Shahbazi M.N. et al.Self-organization of the human embryo in the absence of maternal tissues.Nat. Cell Biol. 2016; 18: 700-708Crossref PubMed Scopus (325) Google Scholar], whereas the cells on the ventral part keep their goblet morphology and develop into late epiblasts [6.Xiang L. et al.A developmental of human PubMed Scopus Google At the cells form the with PE At the epiblast into The to form the which also of a on the ventral part of the this embryonic is the Figure 1A in At the human embryo the gastrulation is a event in early embryonic development because the for three germ layers and the body embryo at the gastrulation stage with three germ layers is a embryonic gastrulation with the of the at the of epiblasts on the of cells and The the of the body and a for the of epiblast the of and the of epiblasts the Figure 1A in The major of human and late gastrulation have been et The embryo and its Biol. 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