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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 -
Development (Cambridge, England) Jul 2012A segmented body plan is fundamental to all vertebrate species and this bestows both rigidity and flexibility on the body. Segmentation is initiated through the process... (Review)
Review
A segmented body plan is fundamental to all vertebrate species and this bestows both rigidity and flexibility on the body. Segmentation is initiated through the process of somitogenesis. This article aims to provide a broad and balanced cross-species overview of somitogenesis and to highlight the key molecular and cellular events involved in each stage of segmentation. We highlight where our understanding of this multifaceted process relies on strong experimental evidence as well as those aspects where our understanding still relies largely on models.
Topics: Animals; Biological Clocks; Body Patterning; Embryonic Development; Gene Expression Regulation, Developmental; Humans; Somites
PubMed: 22736241
DOI: 10.1242/dev.069310 -
Seminars in Cell & Developmental Biology Nov 2020The body axis of vertebrates is subdivided into repetitive compartments called somites, which give rise primarily to the segmented architecture of the musculoskeletal... (Review)
Review
The body axis of vertebrates is subdivided into repetitive compartments called somites, which give rise primarily to the segmented architecture of the musculoskeletal system in the adult body. Somites form in a sequential and rhythmic manner in embryos and a physical boundary separates each somite from the rest of the unsegmented tissue and adjoining somites. Precise positioning of somite boundaries and determination of boundary cell fate in a select group of cells is thought to be driven by gene expression patterns and morphogen gradients. This pre-patterning step is followed by a mechanical process involving actomyosin activation in boundary cells and formation of an extracellular matrix that results in morphological boundary formation. While genes involved in somite boundary formation have been identified, there are many open questions about the underlying pre-patterning dynamics and mechanics and how these processes are coupled to generate a morphological boundary. Here, focusing on segmentation of zebrafish embryos as a model, we review pre-patterning processes critical for boundary formation and how cytoskeletal activity drives tissue separation. Our outlook is that this system holds exciting new avenues for unearthing general principles of boundary formation in developing embryos.
Topics: Animals; Biological Evolution; Body Patterning; Embryo, Nonmammalian; Models, Biological; Somites; Zebrafish
PubMed: 32444288
DOI: 10.1016/j.semcdb.2020.04.014 -
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 -
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 -
Developmental Dynamics : An Official... Nov 2000A full understanding of somite development requires knowledge of the molecular genetic pathways for cell determination as well as the cellular behaviors that underlie... (Comparative Study)
Comparative Study Review
A full understanding of somite development requires knowledge of the molecular genetic pathways for cell determination as well as the cellular behaviors that underlie segmentation, somite epithelialization, and somite patterning. The zebrafish has long been recognized as an ideal organism for cellular and histological studies of somite patterning. In recent years, genetics has proven to be a very powerful complementary approach to these embryological studies, as genetic screens for zebrafish mutants defective in somitogenesis have identified over 50 genes that are necessary for normal somite development. Zebrafish is thus an ideal system in which to analyze the role of specific gene products in regulating the cell behaviors that underlie somite development. We review what is currently known about zebrafish somite development and compare it where appropriate to somite development in chick and mouse. We discuss the processes of segmentation and somite epithelialization, and then review the patterning of cell types within the somite. We show directly, for the first time, that muscle cell and sclerotome migrations occur at the same time. We end with a look at the many questions about somitogenesis that are still unanswered.
Topics: Animals; Biological Clocks; Body Patterning; Cell Differentiation; Cell Movement; Chick Embryo; Gene Expression Regulation, Developmental; Mesoderm; Mice; Muscles; Mutation; Somites; Species Specificity; Zebrafish
PubMed: 11066087
DOI: 10.1002/1097-0177(2000)9999:9999<::AID-DVDY1065>3.0.CO;2-A -
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 -
Nature Communications Apr 2023The metameric pattern of somites is created based on oscillatory expression of clock genes in presomitic mesoderm. However, the mechanism for converting the dynamic...
The metameric pattern of somites is created based on oscillatory expression of clock genes in presomitic mesoderm. However, the mechanism for converting the dynamic oscillation to a static pattern of somites is still unclear. Here, we provide evidence that Ripply/Tbx6 machinery is a key regulator of this conversion. Ripply1/Ripply2-mediated removal of Tbx6 protein defines somite boundary and also leads to cessation of clock gene expression in zebrafish embryos. On the other hand, activation of ripply1/ripply2 mRNA and protein expression is periodically regulated by clock oscillation in conjunction with an Erk signaling gradient. Whereas Ripply protein decreases rapidly in embryos, Ripply-triggered Tbx6 suppression persists long enough to complete somite boundary formation. Mathematical modeling shows that a molecular network based on results of this study can reproduce dynamic-to-static conversion in somitogenesis. Furthermore, simulations with this model suggest that sustained suppression of Tbx6 caused by Ripply is crucial in this conversion.
Topics: Animals; Somites; Zebrafish; T-Box Domain Proteins; Mesoderm; Zebrafish Proteins; Gene Expression Regulation, Developmental
PubMed: 37055428
DOI: 10.1038/s41467-023-37745-w -
Science (New York, N.Y.) Feb 2014The formation of body segments (somites) in vertebrate embryos is accompanied by molecular oscillations (segmentation clock). Interaction of this oscillator with a wave...
The formation of body segments (somites) in vertebrate embryos is accompanied by molecular oscillations (segmentation clock). Interaction of this oscillator with a wave traveling along the body axis (the clock-and-wavefront model) is generally believed to control somite number, size, and axial identity. Here we show that a clock-and-wavefront mechanism is unnecessary for somite formation. Non-somite mesoderm treated with Noggin generates many somites that form simultaneously, without cyclic expression of Notch-pathway genes, yet have normal size, shape, and fate. These somites have axial identity: The Hox code is fixed independently of somite fate. However, these somites are not subdivided into rostral and caudal halves, which is necessary for neural segmentation. We propose that somites are self-organizing structures whose size and shape is controlled by local cell-cell interactions.
Topics: Animals; Bone Morphogenetic Proteins; CLOCK Proteins; Carrier Proteins; Cell Communication; Circadian Clocks; Gene Expression Regulation, Developmental; Homeodomain Proteins; Metabolic Networks and Pathways; Quail; Receptors, Notch; Somites
PubMed: 24407478
DOI: 10.1126/science.1247575 -
Developmental Cell Oct 2023The mammalian body plan is shaped by rhythmic segmentation of mesoderm into somites, which are transient embryonic structures that form down each side of the neural...
The mammalian body plan is shaped by rhythmic segmentation of mesoderm into somites, which are transient embryonic structures that form down each side of the neural tube. We have analyzed the genome-wide transcriptional and chromatin dynamics occurring within nascent somites, from early inception of somitogenesis to the latest stages of body plan establishment. We created matched gene expression and open chromatin maps for the three leading pairs of somites at six time points during mouse embryonic development. We show that the rate of somite differentiation accelerates as development progresses. We identified a conserved maturation program followed by all somites, but somites from more developed embryos concomitantly switch on differentiation programs from derivative cell lineages soon after segmentation. Integrated analysis of the somitic transcriptional and chromatin activities identified opposing regulatory modules controlling the onset of differentiation. Our results provide a powerful, high-resolution view of the molecular genetics underlying somitic development in mammals.
Topics: Pregnancy; Female; Mice; Animals; Somites; Embryonic Development; Mesoderm; Cell Differentiation; Chromatin; Mammals
PubMed: 37499658
DOI: 10.1016/j.devcel.2023.07.003