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Developmental Cell Jan 2022There has been recent renewed interest in studying human early embryonic development. The advent of improved culture conditions to maintain blastocysts in vitro for an... (Review)
Review
There has been recent renewed interest in studying human early embryonic development. The advent of improved culture conditions to maintain blastocysts in vitro for an extended period and the emerging stem-cell-based models of the blastocyst and peri-implantation embryos have provided new information that is relevant to early human embryogenesis. However, the mechanism of lineage development and embryonic patterning, and the molecular pathways involved in their regulation, are still not well understood. Interest in human embryonic development has been reinvigorated recently given numerous technical advances. In this review, Rossant and Tam discuss new insights into human embryogenesis gathered from successes in culturing human embryos in vitro and stem-cell-based embryo models. Then they outline what questions still need answering.
Topics: Blastocyst; Body Patterning; Cell Lineage; Embryo Culture Techniques; Embryo, Mammalian; Embryonic Development; Embryonic Stem Cells; Gastrulation; Gene Expression Regulation, Developmental; Humans
PubMed: 35077679
DOI: 10.1016/j.devcel.2021.12.022 -
Trends in Cell Biology Jan 2022The basic body plan of the mammalian embryo is established through gastrulation, a pivotal early postimplantation event during which the three major germ layers... (Review)
Review
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.
Topics: Animals; Embryo, Mammalian; Embryonic Development; Gastrulation; Humans; Mammals
PubMed: 34417090
DOI: 10.1016/j.tcb.2021.07.008 -
Trends in Biochemical Sciences Jan 2021Hippo pathway components are structurally and functionally conserved and are notable for their role in controlling organ size. More diverse functions of the Hippo... (Review)
Review
Hippo pathway components are structurally and functionally conserved and are notable for their role in controlling organ size. More diverse functions of the Hippo pathway have been recognized, including development, tissue homeostasis, wound healing and regeneration, immunity, and tumorigenesis. During embryogenesis, different signaling pathways are repeatedly and cooperatively activated, leading to differential gene expression in specific developmental contexts. In this article, we present an overview on the regulation and function of the Hippo pathway in mammalian early development. We introduce the Hippo pathway components and major upstream signals that act through this pathway to influence embryogenesis. We also discuss the roles of Hippo pathway in tissue specification and organ development during organogenesis.
Topics: Animals; Embryonic Development; Hippo Signaling Pathway; Humans; Protein Serine-Threonine Kinases; Signal Transduction
PubMed: 32928629
DOI: 10.1016/j.tibs.2020.08.008 -
Molecules (Basel, Switzerland) Jun 2021Folates have a pterine core structure and high metabolic activity due to their ability to accept electrons and react with O-, S-, N-, C-bounds. Folates play a role as... (Review)
Review
Folates have a pterine core structure and high metabolic activity due to their ability to accept electrons and react with O-, S-, N-, C-bounds. Folates play a role as cofactors in essential one-carbon pathways donating methyl-groups to choline phospholipids, creatine, epinephrine, DNA. Compounds similar to folates are ubiquitous and have been found in different animals, plants, and microorganisms. Folates enter the body from the diet and are also synthesized by intestinal bacteria with consequent adsorption from the colon. Three types of folate and antifolate cellular transporters have been found, differing in tissue localization, substrate affinity, type of transferring, and optimal pH for function. Laboratory criteria of folate deficiency are accepted by WHO. Severe folate deficiencies, manifesting in early life, are seen in hereditary folate malabsorption and cerebral folate deficiency. Acquired folate deficiency is quite common and is associated with poor diet and malabsorption, alcohol consumption, obesity, and kidney failure. Given the observational data that folates have a protective effect against neural tube defects, ischemic events, and cancer, food folic acid fortification was introduced in many countries. However, high physiological folate concentrations and folate overload may increase the risk of impaired brain development in embryogenesis and possess a growth advantage for precancerous altered cells.
Topics: Animals; Brain; Embryonic Development; Folic Acid; Folic Acid Deficiency; Humans; Neoplasms; Precancerous Conditions
PubMed: 34207319
DOI: 10.3390/molecules26123731 -
Cell Stem Cell Dec 2023Studies of mammalian development have advanced our understanding of the genetic, epigenetic, and cellular processes that orchestrate embryogenesis and have uncovered new... (Review)
Review
Studies of mammalian development have advanced our understanding of the genetic, epigenetic, and cellular processes that orchestrate embryogenesis and have uncovered new insights into the unique aspects of human embryogenesis. Recent studies have now produced the first epigenetic maps of early human embryogenesis, stimulating new ideas about epigenetic reprogramming, cell fate control, and the potential mechanisms underpinning developmental plasticity in human embryos. In this review, we discuss these new insights into the epigenetic regulation of early human development and the importance of these processes for safeguarding development. We also highlight unanswered questions and key challenges that remain to be addressed.
Topics: Humans; DNA Methylation; Embryo, Mammalian; Embryonic Development; Epigenesis, Genetic
PubMed: 37858333
DOI: 10.1016/j.stem.2023.09.010 -
Cell Apr 2021How are individual cell behaviors coordinated toward invariant large-scale anatomical outcomes in development and regeneration despite unpredictable perturbations?... (Review)
Review
How are individual cell behaviors coordinated toward invariant large-scale anatomical outcomes in development and regeneration despite unpredictable perturbations? Endogenous distributions of membrane potentials, produced by ion channels and gap junctions, are present across all tissues. These bioelectrical networks process morphogenetic information that controls gene expression, enabling cell collectives to make decisions about large-scale growth and form. Recent progress in the analysis and computational modeling of developmental bioelectric circuits and channelopathies reveals how cellular collectives cooperate toward organ-level structural order. These advances suggest a roadmap for exploiting bioelectric signaling for interventions addressing developmental disorders, regenerative medicine, cancer reprogramming, and synthetic bioengineering.
Topics: Animals; Electrophysiological Phenomena; Embryonic Development; Humans; Ion Channels; Models, Biological; Neoplasms; Regenerative Medicine; Signal Transduction
PubMed: 33826908
DOI: 10.1016/j.cell.2021.02.034 -
Cell Sep 2022In vitro cultured stem cells with distinct developmental capacities can contribute to embryonic or extraembryonic tissues after microinjection into pre-implantation...
In vitro cultured stem cells with distinct developmental capacities can contribute to embryonic or extraembryonic tissues after microinjection into pre-implantation mammalian embryos. However, whether cultured stem cells can independently give rise to entire gastrulating embryo-like structures with embryonic and extraembryonic compartments remains unknown. Here, we adapt a recently established platform for prolonged ex utero growth of natural embryos to generate mouse post-gastrulation synthetic whole embryo models (sEmbryos), with both embryonic and extraembryonic compartments, starting solely from naive ESCs. This was achieved by co-aggregating non-transduced ESCs, with naive ESCs transiently expressing Cdx2 or Gata4 to promote their priming toward trophectoderm and primitive endoderm lineages, respectively. sEmbryos adequately accomplish gastrulation, advance through key developmental milestones, and develop organ progenitors within complex extraembryonic compartments similar to E8.5 stage mouse embryos. Our findings highlight the plastic potential of naive pluripotent cells to self-organize and functionally reconstitute and model the entire mammalian embryo beyond gastrulation.
Topics: Animals; Cell Differentiation; Embryo, Mammalian; Embryonic Development; Embryonic Stem Cells; Endoderm; Gastrulation; Mammals; Mice
PubMed: 35988542
DOI: 10.1016/j.cell.2022.07.028 -
Nature Reviews. Molecular Cell Biology Oct 2019Histone methylation can occur at various sites in histone proteins, primarily on lysine and arginine residues, and it can be governed by multiple positive and negative... (Review)
Review
Histone methylation can occur at various sites in histone proteins, primarily on lysine and arginine residues, and it can be governed by multiple positive and negative regulators, even at a single site, to either activate or repress transcription. It is now apparent that histone methylation is critical for almost all stages of development, and its proper regulation is essential for ensuring the coordinated expression of gene networks that govern pluripotency, body patterning and differentiation along appropriate lineages and organogenesis. Notably, developmental histone methylation is highly dynamic. Early embryonic systems display unique histone methylation patterns, prominently including the presence of bivalent (both gene-activating and gene-repressive) marks at lineage-specific genes that resolve to monovalent marks during differentiation, which ensures that appropriate genes are expressed in each tissue type. Studies of the effects of methylation on embryonic stem cell pluripotency and differentiation have helped to elucidate the developmental roles of histone methylation. It has been revealed that methylation and demethylation of both activating and repressive marks are essential for establishing embryonic and extra-embryonic lineages, for ensuring gene dosage compensation via genomic imprinting and for establishing body patterning via HOX gene regulation. Not surprisingly, aberrant methylation during embryogenesis can lead to defects in body patterning and in the development of specific organs. Human genetic disorders arising from mutations in histone methylation regulators have revealed their important roles in the developing skeletal and nervous systems, and they highlight the overlapping and unique roles of different patterns of methylation in ensuring proper development.
Topics: Animals; Body Patterning; Cell Differentiation; Embryonic Development; Gene Expression Regulation, Developmental; Histones; Humans; Methylation; Pluripotent Stem Cells; Protein Processing, Post-Translational
PubMed: 31267065
DOI: 10.1038/s41580-019-0151-1 -
Developmental Cell May 2022A major challenge in understanding vertebrate embryogenesis is the lack of topographical transcriptomic information that can help correlate microenvironmental cues...
A major challenge in understanding vertebrate embryogenesis is the lack of topographical transcriptomic information that can help correlate microenvironmental cues within the hierarchy of cell-fate decisions. Here, we employed Stereo-seq to profile 91 zebrafish embryo sections covering six critical time points during the first 24 h of development, obtaining a total of 152,977 spots at a resolution of 10 × 10 × 15 μm (close to cellular size) with spatial coordinates. Meanwhile, we identified spatial modules and co-varying genes for specific tissue organizations. By performing the integrated analysis of the Stereo-seq and scRNA-seq data from each time point, we reconstructed the spatially resolved developmental trajectories of cell-fate transitions and molecular changes during zebrafish embryogenesis. We further investigated the spatial distribution of ligand-receptor pairs and identified potentially important interactions during zebrafish embryo development. Our study constitutes a fundamental reference for further studies aiming to understand vertebrate development.
Topics: Animals; Embryo, Mammalian; Embryonic Development; Gene Expression Profiling; Gene Expression Regulation, Developmental; Transcriptome; Zebrafish
PubMed: 35512701
DOI: 10.1016/j.devcel.2022.04.009 -
Development (Cambridge, England) Jul 2020Gene regulatory networks and tissue morphogenetic events drive the emergence of shape and function: the pillars of embryo development. Although model systems offer a... (Review)
Review
Gene regulatory networks and tissue morphogenetic events drive the emergence of shape and function: the pillars of embryo development. Although model systems offer a window into the molecular biology of cell fate and tissue shape, mechanistic studies of our own development have so far been technically and ethically challenging. However, recent technical developments provide the tools to describe, manipulate and mimic human embryos in a dish, thus opening a new avenue to exploring human development. Here, I discuss the evidence that supports a role for the crosstalk between cell fate and tissue shape during early human embryogenesis. This is a critical developmental period, when the body plan is laid out and many pregnancies fail. Dissecting the basic mechanisms that coordinate cell fate and tissue shape will generate an integrated understanding of early embryogenesis and new strategies for therapeutic intervention in early pregnancy loss.
Topics: Aneuploidy; Cell Cycle Proteins; Cell Differentiation; Embryo, Mammalian; Embryonic Development; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Humans; Morphogenesis; Transcription Factors
PubMed: 32680920
DOI: 10.1242/dev.190629