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Bone Nov 2015The development of the vertebrate skeleton reflects its evolutionary history. Cartilage formation came before biomineralization and a head skeleton evolved before the... (Review)
Review
The development of the vertebrate skeleton reflects its evolutionary history. Cartilage formation came before biomineralization and a head skeleton evolved before the formation of axial and appendicular skeletal structures. This review describes the processes that result in endochondral and intramembranous ossification, the important roles of growth and transcription factors, and the consequences of mutations in some of the genes involved. Following a summary of the origin of cartilage, muscle, and tendon cell lineages in the axial skeleton, we discuss the role of muscle forces in the formation of skeletal architecture and assembly of musculoskeletal functional units. Finally, ontogenetic patterning of bones in response to mechanical loading is reviewed.This article is part of a Special Issue entitled "Muscle Bone Interactions".
Topics: Animals; Bone Development; Chondrogenesis; Humans; Osteogenesis; Tendons; Transcription Factors
PubMed: 26453494
DOI: 10.1016/j.bone.2015.04.035 -
Nature Oct 2022Embryonic stem (ES) cells can undergo many aspects of mammalian embryogenesis in vitro, but their developmental potential is substantially extended by interactions with...
Embryonic stem (ES) cells can undergo many aspects of mammalian embryogenesis in vitro, but their developmental potential is substantially extended by interactions with extraembryonic stem cells, including trophoblast stem (TS) cells, extraembryonic endoderm stem (XEN) cells and inducible XEN (iXEN) cells. Here we assembled stem cell-derived embryos in vitro from mouse ES cells, TS cells and iXEN cells and showed that they recapitulate the development of whole natural mouse embryo in utero up to day 8.5 post-fertilization. Our embryo model displays headfolds with defined forebrain and midbrain regions and develops a beating heart-like structure, a trunk comprising a neural tube and somites, a tail bud containing neuromesodermal progenitors, a gut tube, and primordial germ cells. This complete embryo model develops within an extraembryonic yolk sac that initiates blood island development. Notably, we demonstrate that the neurulating embryo model assembled from Pax6-knockout ES cells aggregated with wild-type TS cells and iXEN cells recapitulates the ventral domain expansion of the neural tube that occurs in natural, ubiquitous Pax6-knockout embryos. Thus, these complete embryoids are a powerful in vitro model for dissecting the roles of diverse cell lineages and genes in development. Our results demonstrate the self-organization ability of ES cells and two types of extraembryonic stem cells to reconstitute mammalian development through and beyond gastrulation to neurulation and early organogenesis.
Topics: Animals; Cell Lineage; Embryo, Mammalian; Embryonic Stem Cells; Endoderm; Gastrulation; Heart; Mesencephalon; Mice; Models, Biological; Neural Tube; Neurulation; Organogenesis; PAX6 Transcription Factor; Prosencephalon; Somites
PubMed: 36007540
DOI: 10.1038/s41586-022-05246-3 -
Nature Feb 2023The vertebrate body displays a segmental organization that is most conspicuous in the periodic organization of the vertebral column and peripheral nerves. This metameric...
The vertebrate body displays a segmental organization that is most conspicuous in the periodic organization of the vertebral column and peripheral nerves. This metameric organization is first implemented when somites, which contain the precursors of skeletal muscles and vertebrae, are rhythmically generated from the presomitic mesoderm. Somites then become subdivided into anterior and posterior compartments that are essential for vertebral formation and segmental patterning of the peripheral nervous system. How this key somitic subdivision is established remains poorly understood. Here we introduce three-dimensional culture systems of human pluripotent stem cells called somitoids and segmentoids, which recapitulate the formation of somite-like structures with anteroposterior identity. We identify a key function of the segmentation clock in converting temporal rhythmicity into the spatial regularity of anterior and posterior somitic compartments. We show that an initial 'salt and pepper' expression of the segmentation gene MESP2 in the newly formed segment is transformed into compartments of anterior and posterior identity through an active cell-sorting mechanism. Our research demonstrates that the major patterning modules that are involved in somitogenesis, including the clock and wavefront, anteroposterior polarity patterning and somite epithelialization, can be dissociated and operate independently in our in vitro systems. Together, we define a framework for the symmetry-breaking process that initiates somite polarity patterning. Our work provides a platform for decoding general principles of somitogenesis and advancing knowledge of human development.
Topics: Humans; Body Patterning; Cell Culture Techniques, Three Dimensional; In Vitro Techniques; Somites; Spine; Biological Clocks; Epithelium
PubMed: 36543321
DOI: 10.1038/s41586-022-05655-4 -
Cell Feb 2023Axial development of mammals involves coordinated morphogenetic events, including axial elongation, somitogenesis, and neural tube formation. To gain insight into the...
Axial development of mammals involves coordinated morphogenetic events, including axial elongation, somitogenesis, and neural tube formation. To gain insight into the signals controlling the dynamics of human axial morphogenesis, we generated axially elongating organoids by inducing anteroposterior symmetry breaking of spatially coupled epithelial cysts derived from human pluripotent stem cells. Each organoid was composed of a neural tube flanked by presomitic mesoderm sequentially segmented into somites. Periodic activation of the somite differentiation gene MESP2 coincided in space and time with anteriorly traveling segmentation clock waves in the presomitic mesoderm of the organoids, recapitulating critical aspects of somitogenesis. Timed perturbations demonstrated that FGF and WNT signaling play distinct roles in axial elongation and somitogenesis, and that FGF signaling gradients drive segmentation clock waves. By generating and perturbing organoids that robustly recapitulate the architecture of multiple axial tissues in human embryos, this work offers a means to dissect mechanisms underlying human embryogenesis.
Topics: Animals; Humans; Body Patterning; Embryonic Development; Gene Expression Regulation, Developmental; Mammals; Mesoderm; Morphogenesis; Somites; Wnt Signaling Pathway; Organoids
PubMed: 36657441
DOI: 10.1016/j.cell.2022.12.042 -
BMC Biology Feb 2023Skeletal muscle development is a multistep process whose understanding is central in a broad range of fields and applications, from the potential medical value to human...
BACKGROUND
Skeletal muscle development is a multistep process whose understanding is central in a broad range of fields and applications, from the potential medical value to human society, to its economic value associated with improvement of agricultural animals. Skeletal muscle initiates in the somites, with muscle precursor cells generated in the dermomyotome and dermomyotome-derived myotome before muscle differentiation ensues, a developmentally regulated process that is well characterized in model organisms. However, the regulation of skeletal muscle ontogeny during embryonic development remains poorly defined in farm animals, for instance in pig. Here, we profiled gene expression and chromatin accessibility in developing pig somites and myotomes at single-cell resolution.
RESULTS
We identified myogenic cells and other cell types and constructed a differentiation trajectory of pig skeletal muscle ontogeny. Along this trajectory, the dynamic changes in gene expression and chromatin accessibility coincided with the activities of distinct cell type-specific transcription factors. Some novel genes upregulated along the differentiation trajectory showed higher expression levels in muscular dystrophy mice than that in healthy mice, suggesting their involvement in myogenesis. Integrative analysis of chromatin accessibility, gene expression data, and in vitro experiments identified EGR1 and RHOB as critical regulators of pig embryonic myogenesis.
CONCLUSIONS
Collectively, our results enhance our understanding of the molecular and cellular dynamics in pig embryonic myogenesis and offer a high-quality resource for the further study of pig skeletal muscle development and human muscle disease.
Topics: Animals; Mice; Cell Differentiation; Chromatin; Chromatin Immunoprecipitation Sequencing; Gene Expression Regulation, Developmental; Muscle Development; Muscle, Skeletal; Single-Cell Analysis; Single-Cell Gene Expression Analysis; Swine
PubMed: 36726129
DOI: 10.1186/s12915-023-01519-z -
The International Journal of... 2018Striated muscle is the most abundant tissue in the body of vertebrates and it forms, together with the skeleton, the locomotory system required both for movement and the... (Review)
Review
Striated muscle is the most abundant tissue in the body of vertebrates and it forms, together with the skeleton, the locomotory system required both for movement and the creation of the specific body shape of a species. Research on the embryonic development of muscles has a long tradition both in classical embryology and in molecular developmental biology. While the gene networks regulating muscle development have been discovered mostly in the mouse through genetics, our knowledge on cell lineages, muscle morphogenesis and tissue interactions regulating their formation is to a large extent based on the use of the avian model. This review highlights present knowledge of the development of skeletal muscle in vertebrate embryos. Special focus will be placed on the contributions from chicken and quail embryo model systems.
Topics: Animals; Cell Differentiation; Cell Lineage; Chick Embryo; Chickens; Electroporation; Embryonic Development; Mesoderm; Mice; Morphogenesis; Muscle Development; Quail; Signal Transduction; Somites; Stem Cells
PubMed: 29616720
DOI: 10.1387/ijdb.170312cm -
Cold Spring Harbor Protocols Feb 2019In 1924, Hans Spemann and Hilde Mangold (née Pröscholdt) published their famous work describing the transplantation of dorsal blastopore lip of one newt gastrula...
In 1924, Hans Spemann and Hilde Mangold (née Pröscholdt) published their famous work describing the transplantation of dorsal blastopore lip of one newt gastrula embryo onto the ventral side of a host embryo at the same stage. They performed these grafts using two newt species with different pigmentation ( and ) to follow the fate of the grafted tissue. These experiments resulted in the development of conjoined twins attached through their belly. Because of the difference in embryo pigmentation between the two species, they determined that the bulk of the secondary embryo arose from the host embryo while the grafted tissue per se gave increase to the notochord and a few somitic cells. This meant that the dorsal blastopore lip was able to organize an almost complete embryo out of ventral tissue. The dorsal blastopore lip is now called the Spemann-Mangold organizer. Here, we describe a simple yet efficient protocol to perform these grafts using the anuran
Topics: Animals; Fetal Tissue Transplantation; Gastrula; Organizers, Embryonic; Transplantation, Homologous; Xenopus
PubMed: 29321278
DOI: 10.1101/pdb.prot097345 -
The International Journal of... 2018Somites are epithelial blocks of paraxial mesoderm that define the vertebrate embryonic segments. They are responsible for imposing the metameric pattern observed in... (Review)
Review
Somites are epithelial blocks of paraxial mesoderm that define the vertebrate embryonic segments. They are responsible for imposing the metameric pattern observed in many tissues of the adult such as the vertebrae, and they give rise to most of the axial skeleton and skeletal muscles of the trunk. Due to its easy accessibility in the egg, the chicken embryo has provided an ideal model to study somite development. Somites were first described in the chicken embryo by Malpighi in the 17 century, soon after the invention of the microscope. Most of the major concepts relating to somite segmentation and differentiation result from studies performed in the chicken embryo (Brand-Saberi and Christ, 2000). In this review, we will discuss how studies on somites in avian embryos have contributed to our understanding of key developmental processes such as segmentation, control of bilateral symmetry or axis regionalization.
Topics: Animals; Body Patterning; Cell Differentiation; Cell Lineage; Chick Embryo; Chickens; Embryology; Embryonic Development; Gene Expression Regulation, Developmental; History, 17th Century; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Mesoderm; Mice; Somites; Vertebrates; Zebrafish
PubMed: 29616740
DOI: 10.1387/ijdb.180036op -
Cell Jul 2016Stem-cell differentiation to desired lineages requires navigating alternating developmental paths that often lead to unwanted cell types. Hence, comprehensive...
Stem-cell differentiation to desired lineages requires navigating alternating developmental paths that often lead to unwanted cell types. Hence, comprehensive developmental roadmaps are crucial to channel stem-cell differentiation toward desired fates. To this end, here, we map bifurcating lineage choices leading from pluripotency to 12 human mesodermal lineages, including bone, muscle, and heart. We defined the extrinsic signals controlling each binary lineage decision, enabling us to logically block differentiation toward unwanted fates and rapidly steer pluripotent stem cells toward 80%-99% pure human mesodermal lineages at most branchpoints. This strategy enabled the generation of human bone and heart progenitors that could engraft in respective in vivo models. Mapping stepwise chromatin and single-cell gene expression changes in mesoderm development uncovered somite segmentation, a previously unobservable human embryonic event transiently marked by HOPX expression. Collectively, this roadmap enables navigation of mesodermal development to produce transplantable human tissue progenitors and uncover developmental processes. VIDEO ABSTRACT.
Topics: Bone Morphogenetic Proteins; Bone and Bones; Heart; Homeodomain Proteins; Humans; Mesoderm; Myocytes, Cardiac; Pluripotent Stem Cells; Primitive Streak; Signal Transduction; Single-Cell Analysis; Somites; Stem Cells; Tumor Suppressor Proteins; Wnt Proteins
PubMed: 27419872
DOI: 10.1016/j.cell.2016.06.011 -
Cellular and Molecular Life Sciences :... Feb 2021During embryogenesis, the processes that control how cells differentiate and interact to form particular tissues and organs with precise timing and shape are of... (Review)
Review
During embryogenesis, the processes that control how cells differentiate and interact to form particular tissues and organs with precise timing and shape are of fundamental importance. One prominent example of such processes is vertebrate somitogenesis, which is governed by a molecular oscillator called the segmentation clock. The segmentation clock system is initiated in the presomitic mesoderm in which a set of genes and signaling pathways exhibit coordinated spatiotemporal dynamics to establish regularly spaced boundaries along the body axis; these boundaries provide a blueprint for the development of segment-like structures such as spines and skeletal muscles. The highly complex and dynamic nature of this in vivo event and the design principles and their regulation in both normal and abnormal embryogenesis are not fully understood. Recently, live-imaging has been used to quantitatively analyze the dynamics of selected components of the circuit, particularly in combination with well-designed experiments to perturb the system. Here, we review recent progress from studies using live imaging and manipulation, including attempts to recapitulate the segmentation clock in vitro. In combination with mathematical modeling, these techniques have become essential for disclosing novel aspects of the clock.
Topics: Biological Clocks; Body Patterning; Cell Differentiation; Embryonic Development; Gene Expression Regulation, Developmental; Humans; Mesoderm; Models, Theoretical; Signal Transduction; Somites
PubMed: 33015720
DOI: 10.1007/s00018-020-03655-z