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Nature Communications Jan 2024Embryonic cells exhibit diverse metabolic states. Recent studies have demonstrated that metabolic reprogramming drives changes in cell identity by affecting gene...
Embryonic cells exhibit diverse metabolic states. Recent studies have demonstrated that metabolic reprogramming drives changes in cell identity by affecting gene expression. However, the connection between cellular metabolism and gene expression remains poorly understood. Here we report that glycolysis-regulated histone lactylation couples the metabolic state of embryonic cells with chromatin organization and gene regulatory network (GRN) activation. We found that lactylation marks genomic regions of glycolytic embryonic tissues, like the neural crest (NC) and pre-somitic mesoderm. Histone lactylation occurs in the loci of NC genes as these cells upregulate glycolysis. This process promotes the accessibility of active enhancers and the deployment of the NC GRN. Reducing the deposition of the mark by targeting LDHA/B leads to the downregulation of NC genes and the impairment of cell migration. The deposition of lactyl-CoA on histones at NC enhancers is supported by a mechanism that involves transcription factors SOX9 and YAP/TEAD. These findings define an epigenetic mechanism that integrates cellular metabolism with the GRNs that orchestrate embryonic development.
Topics: Histones; Gene Regulatory Networks; Transcription Factors; Embryonic Development; Mesoderm
PubMed: 38167340
DOI: 10.1038/s41467-023-44121-1 -
Cells & Development Dec 2021Early in animal development many cells are conditionally specified based on observations that those cells can be directed toward alternate fates. The endomesoderm is so... (Review)
Review
Early in animal development many cells are conditionally specified based on observations that those cells can be directed toward alternate fates. The endomesoderm is so named because early specification produces cells that often have been observed to simultaneously express both early endoderm and mesoderm transcription factors. Experiments with these cells demonstrate that their progeny can directed entirely toward endoderm or mesoderm, whereas normally they establish both germ layers. This review examines the mechanisms that initiate the conditional endomesoderm state, its metastability, and the mechanisms that resolve that state into definitive endoderm and mesoderm.
Topics: Animals; Embryo, Nonmammalian; Endoderm; Mesoderm; Sea Urchins; Signal Transduction
PubMed: 34610899
DOI: 10.1016/j.cdev.2021.203731 -
Development (Cambridge, England) Jun 2020The lateral plate mesoderm (LPM) forms the progenitor cells that constitute the heart and cardiovascular system, blood, kidneys, smooth muscle lineage and limb skeleton... (Review)
Review
The lateral plate mesoderm (LPM) forms the progenitor cells that constitute the heart and cardiovascular system, blood, kidneys, smooth muscle lineage and limb skeleton in the developing vertebrate embryo. Despite this central role in development and evolution, the LPM remains challenging to study and to delineate, owing to its lineage complexity and lack of a concise genetic definition. Here, we outline the processes that govern LPM specification, organization, its cell fates and the inferred evolutionary trajectories of LPM-derived tissues. Finally, we discuss the development of seemingly disparate organ systems that share a common LPM origin.
Topics: Animals; Cardiovascular System; Cell Differentiation; Cell Lineage; Embryonic Development; Gene Expression Regulation, Developmental; Humans; Mesoderm; Stem Cells; Transcription Factors
PubMed: 32561665
DOI: 10.1242/dev.175059 -
Current Topics in Developmental Biology 2024For almost a century, developmental biologists have appreciated that the ability of the embryonic organizer to induce and pattern the body plan is intertwined with its... (Review)
Review
For almost a century, developmental biologists have appreciated that the ability of the embryonic organizer to induce and pattern the body plan is intertwined with its differentiation into axial mesoderm. Despite this, we still have a relatively poor understanding of the contribution of axial mesoderm to induction and patterning of different body regions, and the manner in which axial mesoderm-derived information is interpreted in tissues of changing competence. Here, with a particular focus on the nervous system, we review the evidence that axial mesoderm notochord and prechordal mesoderm/mesendoderm act as organizers, discuss how their influence extends through the different axes of the developing organism, and describe how the ability of axial mesoderm to direct morphogenesis impacts on its role as a local organizer.
Topics: Mesoderm; Morphogenesis; Nervous System; Body Patterning; Brain; Face; Germ Layers
PubMed: 38556460
DOI: 10.1016/bs.ctdb.2024.02.007 -
Development (Cambridge, England) Apr 2023During gastrulation, early embryos specify and reorganise the topology of their germ layers. Surprisingly, this fundamental and early process does not appear to be... (Review)
Review
During gastrulation, early embryos specify and reorganise the topology of their germ layers. Surprisingly, this fundamental and early process does not appear to be rigidly constrained by evolutionary pressures; instead, the morphology of gastrulation is highly variable throughout the animal kingdom. Recent experimental results demonstrate that it is possible to generate different alternative gastrulation modes in single organisms, such as in early cnidarian, arthropod and vertebrate embryos. Here, we review the mechanisms that underlie the plasticity of vertebrate gastrulation both when experimentally manipulated and during evolution. Using the insights obtained from these experiments we discuss the effects of the increase in yolk volume on the morphology of gastrulation and provide new insights into two crucial innovations during amniote gastrulation: the transition from a ring-shaped mesoderm domain in anamniotes to a crescent-shaped domain in amniotes, and the evolution of the reptilian blastoporal plate/canal into the avian primitive streak.
Topics: Animals; Gastrulation; Gastrula; Mesoderm; Germ Layers; Primitive Streak
PubMed: 37067451
DOI: 10.1242/dev.200885 -
ELife Jun 2022Advanced imaging techniques reveal details of the interactions between the two layers of the embryonic midgut that influence its ultimate shape.
Advanced imaging techniques reveal details of the interactions between the two layers of the embryonic midgut that influence its ultimate shape.
Topics: Animals; Drosophila; Endoderm; Gene Expression Regulation, Developmental; Mesoderm; Morphogenesis
PubMed: 35771125
DOI: 10.7554/eLife.80416 -
Anatomical Record (Hoboken, N.J. : 2007) Aug 2022The process by which upper respiratory tract structures have changed over deep evolutionary time is, in part, reflected in the process of embryologic development. The...
The process by which upper respiratory tract structures have changed over deep evolutionary time is, in part, reflected in the process of embryologic development. The nasopharynx in particular is a centrally located space bounded by components of the respiratory portion of the nasal cavity, cranial base, soft palate, and Eustachian tube. The development of these components can be understood both in terms of embryologic structures such as the branchial arches and paraxial mesoderm and through fossil evidence dating as far back as the earliest agnathan fish of the Cambrian Period. Understanding both the evolution and development of these structures has been an immeasurable benefit to the otolaryngologist seeking to model disease etiology of both common and rare conditions. This discussion is a primer for those who may be unfamiliar with the central importance of the nasopharynx both in terms of our evolutionary history and early embryological development of vital cranial and upper respiratory tract structures.
Topics: Animals; Biological Evolution; Branchial Region; Developmental Biology; Mesoderm; Nasopharynx; Skull
PubMed: 35665451
DOI: 10.1002/ar.24950 -
Seminars in Cell & Developmental Biology Jul 2022The discovery of mesoderm inducing signals helped usher in the era of molecular developmental biology, and today the mechanisms of mesoderm induction and patterning are... (Review)
Review
The discovery of mesoderm inducing signals helped usher in the era of molecular developmental biology, and today the mechanisms of mesoderm induction and patterning are still intensely studied. Mesoderm induction begins during gastrulation, but recent evidence in vertebrates shows that this process continues after gastrulation in a group of posteriorly localized cells called neuromesodermal progenitors (NMPs). NMPs reside within the post-gastrulation embryonic structure called the tailbud, where they make a lineage decision between ectoderm (spinal cord) and mesoderm. The majority of NMP-derived mesoderm generates somites, but also contributes to lateral mesoderm fates such as endothelium. The discovery of NMPs provides a new paradigm in which to study vertebrate mesoderm induction. This review will discuss mechanisms of mesoderm induction within NMPs, and how they have informed our understanding of mesoderm induction more broadly within vertebrates as well as animal species outside of the vertebrate lineage. Special focus will be given to the signaling networks underlying NMP-derived mesoderm induction and patterning, as well as emerging work on the significance of partial epithelial-mesenchymal states in coordinating cell fate and morphogenesis.
Topics: Animals; Body Patterning; Cell Differentiation; Gastrulation; Gene Expression Regulation, Developmental; Mesoderm; Somites
PubMed: 34840081
DOI: 10.1016/j.semcdb.2021.11.010 -
Development, Growth & Differentiation Jan 2021Human pluripotent stem cells (PSCs) are used as a platform for therapeutic purposes such as cell transplantation therapy and drug discovery. Another motivation for... (Review)
Review
Human pluripotent stem cells (PSCs) are used as a platform for therapeutic purposes such as cell transplantation therapy and drug discovery. Another motivation for studying PSCs is to understand human embryogenesis and development. All cell types that make up the body tissues develop through defined trajectories during embryogenesis. For example, paraxial mesoderm is considered to differentiate into several cell types including skeletal muscle cells, chondrocytes, osteocytes, dermal fibroblasts, and tenocytes. Tenocytes are fibroblast cells that constitute the tendon. The step-wise narrowing fate decisions of paraxial mesoderm in the embryo have been modeled in vitro using PSCs; however, deriving tenocytes from human-induced PSCs and their application in cell therapy have long been challenging. PSC-derived tenocytes can be used for a source of cell transplantation to treat a damaged or ruptured tendon due to injury, disorder, or aging. In this review, we discuss the latest research findings on the use of PSCs for studying the biology of tenocyte development and their application in therapeutic settings.
Topics: Cell Differentiation; Humans; Pluripotent Stem Cells; Tenocytes
PubMed: 33270251
DOI: 10.1111/dgd.12702 -
Experimental & Molecular Medicine Aug 2020Pluripotent stem cells (PSCs) are attractive regenerative therapy tools for skeletal tissues. However, a deep understanding of skeletal development is required in order... (Review)
Review
Pluripotent stem cells (PSCs) are attractive regenerative therapy tools for skeletal tissues. However, a deep understanding of skeletal development is required in order to model this development with PSCs, and for the application of PSCs in clinical settings. Skeletal tissues originate from three types of cell populations: the paraxial mesoderm, lateral plate mesoderm, and neural crest. The paraxial mesoderm gives rise to the sclerotome mainly through somitogenesis. In this process, key developmental processes, including initiation of the segmentation clock, formation of the determination front, and the mesenchymal-epithelial transition, are sequentially coordinated. The sclerotome further forms vertebral columns and contributes to various other tissues, such as tendons, vessels (including the dorsal aorta), and even meninges. To understand the molecular mechanisms underlying these developmental processes, extensive studies have been conducted. These studies have demonstrated that a gradient of activities involving multiple signaling pathways specify the embryonic axis and induce cell-type-specific master transcription factors in a spatiotemporal manner. Moreover, applying the knowledge of mesoderm development, researchers have attempted to recapitulate the in vivo development processes in in vitro settings, using mouse and human PSCs. In this review, we summarize the state-of-the-art understanding of mesoderm development and in vitro modeling of mesoderm development using PSCs. We also discuss future perspectives on the use of PSCs to generate skeletal tissues for basic research and clinical applications.
Topics: Animals; Bone Development; Bone and Bones; Humans; Mesoderm; Pluripotent Stem Cells; Somites; Wound Healing
PubMed: 32788657
DOI: 10.1038/s12276-020-0482-1