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Cells & Development Dec 2021Vertebrate segmentation, the process that generates a regular arrangement of somites and thereby establishes the pattern of the adult body and of the musculoskeletal and... (Review)
Review
Vertebrate segmentation, the process that generates a regular arrangement of somites and thereby establishes the pattern of the adult body and of the musculoskeletal and peripheral nervous systems, was noticed many centuries ago. In the last few decades, there has been renewed interest in the process and especially in the molecular mechanisms that might account for its regularity and other spatial-temporal properties. Several models have been proposed but surprisingly, most of these do not provide clear links between the molecular mechanisms and the cell behaviours that generate the segmental pattern. Here we present a short survey of our current knowledge about the cellular aspects of vertebrate segmentation and the similarities and differences between different vertebrate groups in how they achieve their metameric pattern. Taking these variations into account should help to assess each of the models more appropriately.
Topics: Animals; Body Patterning; Somites; Vertebrates
PubMed: 34391979
DOI: 10.1016/j.cdev.2021.203732 -
International Journal of Molecular... Aug 2021To ensure the formation of a properly patterned embryo, multiple processes must operate harmoniously at sequential phases of development. This is implemented by mutual... (Review)
Review
To ensure the formation of a properly patterned embryo, multiple processes must operate harmoniously at sequential phases of development. This is implemented by mutual interactions between cells and tissues that together regulate the segregation and specification of cells, their growth and morphogenesis. The formation of the spinal cord and paraxial mesoderm derivatives exquisitely illustrate these processes. Following early gastrulation, while the vertebrate body elongates, a population of bipotent neuromesodermal progenitors resident in the posterior region of the embryo generate both neural and mesodermal lineages. At later stages, the somitic mesoderm regulates aspects of neural patterning and differentiation of both central and peripheral neural progenitors. Reciprocally, neural precursors influence the paraxial mesoderm to regulate somite-derived myogenesis and additional processes by distinct mechanisms. Central to this crosstalk is the activity of the axial notochord, which, via sonic hedgehog signaling, plays pivotal roles in neural, skeletal muscle and cartilage ontogeny. Here, we discuss the cellular and molecular basis underlying this complex developmental plan, with a focus on the logic of sonic hedgehog activities in the coordination of the neural-mesodermal axis.
Topics: Animals; Cell Differentiation; Embryonic Stem Cells; Gene Expression Regulation, Developmental; Hedgehog Proteins; Humans; Mesoderm; Neural Tube
PubMed: 34502050
DOI: 10.3390/ijms22179141 -
Nature Communications Dec 2021How tubular organs elongate is poorly understood. We found that attenuated ciliary Hedgehog signaling in the gut wall impaired patterning of the circumferential smooth...
How tubular organs elongate is poorly understood. We found that attenuated ciliary Hedgehog signaling in the gut wall impaired patterning of the circumferential smooth muscle and inhibited proliferation and elongation of developing intestine and esophagus. Similarly, ablation of gut-wall smooth muscle cells reduced lengthening. Disruption of ciliary Hedgehog signaling or removal of smooth muscle reduced residual stress within the gut wall and decreased activity of the mechanotransductive effector YAP. Removing YAP in the mesenchyme also reduced proliferation and elongation, but without affecting smooth muscle formation, suggesting that YAP interprets the smooth muscle-generated force to promote longitudinal growth. Additionally, we developed an intestinal culture system that recapitulates the requirements for cilia and mechanical forces in elongation. Pharmacologically activating YAP in this system restored elongation of cilia-deficient intestines. Thus, our results reveal that ciliary Hedgehog signaling patterns the circumferential smooth muscle to generate radial mechanical forces that activate YAP and elongate the gut.
Topics: Animals; Cell Proliferation; Cilia; Gastrointestinal Tract; Hedgehog Proteins; Mesoderm; Mice; Muscle, Smooth; Myocytes, Smooth Muscle; Protein Serine-Threonine Kinases; Signal Transduction
PubMed: 34893605
DOI: 10.1038/s41467-021-27319-z -
Genetics Jun 2020Mesoderm migration in the embryo is a highly conserved, complex process that is required for the formation of specialized tissues and organs, including the somatic and... (Review)
Review
Mesoderm migration in the embryo is a highly conserved, complex process that is required for the formation of specialized tissues and organs, including the somatic and visceral musculature. In this FlyBook chapter, we will compare and contrast the specification and migration of cells originating from the trunk and caudal mesoderm. Both cell types engage in collective migrations that enable cells to achieve new positions within developing embryos and form distinct tissues. To start, we will discuss specification and early morphogenetic movements of the presumptive mesoderm, then focus on the coordinate movements of the two subtypes trunk mesoderm and caudal visceral mesoderm, ending with a comparison of these processes including general insights gained through study.
Topics: Animals; Cell Movement; Drosophila; Drosophila Proteins; Embryo, Nonmammalian; Gene Expression Regulation, Developmental; Mesoderm; Myoblasts
PubMed: 32487692
DOI: 10.1534/genetics.120.303258 -
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 -
Nature Jun 2022Proper ectodermal patterning during human development requires previously identified transcription factors such as GATA3 and p63, as well as positional signalling from...
Proper ectodermal patterning during human development requires previously identified transcription factors such as GATA3 and p63, as well as positional signalling from regional mesoderm. However, the mechanism by which ectoderm and mesoderm factors act to stably pattern gene expression and lineage commitment remains unclear. Here we identify the protein Gibbin, encoded by the Xia-Gibbs AT-hook DNA-binding-motif-containing 1 (AHDC1) disease gene, as a key regulator of early epithelial morphogenesis. We find that enhancer- or promoter-bound Gibbin interacts with dozens of sequence-specific zinc-finger transcription factors and methyl-CpG-binding proteins to regulate the expression of mesoderm genes. The loss of Gibbin causes an increase in DNA methylation at GATA3-dependent mesodermal genes, resulting in a loss of signalling between developing dermal and epidermal cell types. Notably, Gibbin-mutant human embryonic stem-cell-derived skin organoids lack dermal maturation, resulting in p63-expressing basal cells that possess defective keratinocyte stratification. In vivo chimeric CRISPR mouse mutants reveal a spectrum of Gibbin-dependent developmental patterning defects affecting craniofacial structure, abdominal wall closure and epidermal stratification that mirror patient phenotypes. Our results indicate that the patterning phenotypes seen in Xia-Gibbs and related syndromes derive from abnormal mesoderm maturation as a result of gene-specific DNA methylation decisions.
Topics: Animals; Humans; Mice; Dermis; DNA Methylation; DNA-Binding Proteins; Ectoderm; Embryonic Stem Cells; Epidermal Cells; Epithelial Cells; Epithelium; GATA3 Transcription Factor; Gene Expression Regulation, Developmental; Mesoderm; Morphogenesis; Mutation; Organoids; Trans-Activators; Transcription Factors
PubMed: 35585237
DOI: 10.1038/s41586-022-04727-9 -
Seminars in Cell & Developmental Biology Apr 2020Convergent extension is a fundamental morphogenetic process that underlies not only the generation of the elongated vertebrate body plan from the initially radially... (Review)
Review
Convergent extension is a fundamental morphogenetic process that underlies not only the generation of the elongated vertebrate body plan from the initially radially symmetrical embryo, but also the specific shape changes characteristic of many individual tissues. These tissue shape changes are the result of specific cell behaviors, coordinated in time and space, and affected by the physical properties of the tissue. While mediolateral cell intercalation is the classic cellular mechanism for producing tissue convergence and extension, other cell behaviors can also provide similar tissue-scale distortions or can modulate the effects of mediolateral cell intercalation to sculpt a specific shape. Regulation of regional tissue morphogenesis through planar polarization of the variety of underlying cell behaviors is well-recognized, but as yet is not well understood at the molecular level. Here, we review recent advances in understanding the cellular basis for convergence and extension and its regulation.
Topics: Animals; Embryo, Mammalian; Mesoderm; Morphogenesis
PubMed: 31734039
DOI: 10.1016/j.semcdb.2019.11.002 -
Mechanisms of Development Sep 2020Gastrulation is generally understood as the morphogenetic processes that result in the spatial organization of the blastomere into the three germ layers, ectoderm,... (Review)
Review
Gastrulation is generally understood as the morphogenetic processes that result in the spatial organization of the blastomere into the three germ layers, ectoderm, mesoderm and endoderm. This review summarizes our current knowledge of the morphogenetic mechanisms in Drosophila gastrulation. In addition to the events that drive mesoderm invagination and germband elongation, we pay particular attention to other, less well-known mechanisms including midgut invagination, cephalic furrow formation, dorsal fold formation, and mesoderm layer formation. This review covers topics ranging from the identification and functional characterization of developmental and morphogenetic control genes to the analysis of the physical properties of cells and tissues and the control of cell and tissue mechanics of the morphogenetic movements in the gastrula.
Topics: Animals; Biomechanical Phenomena; Drosophila melanogaster; Ectoderm; Embryo, Nonmammalian; Endoderm; Gastrula; Gastrulation; Gene Expression Regulation, Developmental; Mesoderm; Morphogenesis
PubMed: 32615151
DOI: 10.1016/j.mod.2020.103629 -
Nature Communications Jul 2020Human embryogenesis is hallmarked by two phases of yolk sac development. The primate hypoblast gives rise to a transient primary yolk sac, which is rapidly superseded by... (Review)
Review
Human embryogenesis is hallmarked by two phases of yolk sac development. The primate hypoblast gives rise to a transient primary yolk sac, which is rapidly superseded by a secondary yolk sac during gastrulation. Moreover, primate embryos form extraembryonic mesoderm prior to gastrulation, in contrast to mouse. The function of the primary yolk sac and the origin of extraembryonic mesoderm remain unclear. Here, we hypothesise that the hypoblast-derived primary yolk sac serves as a source for early extraembryonic mesoderm, which is supplemented with mesoderm from the gastrulating embryo. We discuss the intricate relationship between the yolk sac and the primate embryo and highlight the pivotal role of the yolk sac as a multifunctional hub for haematopoiesis, germ cell development and nutritional supply.
Topics: Animals; Cell Differentiation; Embryonic Development; Embryonic Germ Cells; Hematopoiesis; Mesoderm; Primates; Yolk Sac
PubMed: 32724077
DOI: 10.1038/s41467-020-17575-w -
International Journal of Molecular... Mar 2022Cardiovascular development is initiated soon after gastrulation as bilateral precardiac mesoderm is progressively symmetrically determined at both sides of the... (Review)
Review
Cardiovascular development is initiated soon after gastrulation as bilateral precardiac mesoderm is progressively symmetrically determined at both sides of the developing embryo. The precardiac mesoderm subsequently fused at the embryonic midline constituting an embryonic linear heart tube. As development progress, the embryonic heart displays the first sign of left-right asymmetric morphology by the invariably rightward looping of the initial heart tube and prospective embryonic ventricular and atrial chambers emerged. As cardiac development progresses, the atrial and ventricular chambers enlarged and distinct left and right compartments emerge as consequence of the formation of the interatrial and interventricular septa, respectively. The last steps of cardiac morphogenesis are represented by the completion of atrial and ventricular septation, resulting in the configuration of a double circuitry with distinct systemic and pulmonary chambers, each of them with distinct inlets and outlets connections. Over the last decade, our understanding of the contribution of multiple growth factor signaling cascades such as Tgf-beta, Bmp and Wnt signaling as well as of transcriptional regulators to cardiac morphogenesis have greatly enlarged. Recently, a novel layer of complexity has emerged with the discovery of non-coding RNAs, particularly microRNAs and lncRNAs. Herein, we provide a state-of-the-art review of the contribution of non-coding RNAs during cardiac development. microRNAs and lncRNAs have been reported to functional modulate all stages of cardiac morphogenesis, spanning from lateral plate mesoderm formation to outflow tract septation, by modulating major growth factor signaling pathways as well as those transcriptional regulators involved in cardiac development.
Topics: Gene Expression Regulation, Developmental; Heart; Heart Atria; Mesoderm; MicroRNAs; Morphogenesis; Prospective Studies; RNA, Long Noncoding; Transcription Factors; Transforming Growth Factor beta
PubMed: 35269981
DOI: 10.3390/ijms23052839