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Takaaki Matsui - One of the best experts on this subject based on the ideXlab platform.
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Somite boundary determination in normal and clock less vertebrate embryos
Development Growth & Differentiation, 2020Co-Authors: Honda Naoki, Takaaki MatsuiAbstract:Vertebrate segments called Somites are generated by periodic segmentation of the presomitic mesoderm (PSM). In the most accepted theoretical model for Somite segmentation, the clock and wavefront (CW) model, a clock that ticks to determine particular timings and a wavefront that moves posteriorly are presented in the PSM, and Somite positions are determined when the clock meets the posteriorly moving wavefront somewhere in the PSM. Over the last two decades, it has been revealed that the molecular mechanism of the clock and wavefront in vertebrates is based on clock genes including Hes family transcription factors and Notch effectors that oscillate within the PSM to determine particular timings and fibroblast growth factor (FGF) gradients, acting as the posteriorly moving wavefront to determine the position of Somite segmentation. A clock-less condition in the CW model was predicted to form no Somites; however, irregularly sized Somites were still formed in mice and zebrafish, suggesting that this was one of the limitations of the CW model. Recently, we performed interdisciplinary research of experimental and theoretical biological studies and revealed the mechanisms of Somite boundary determination in normal and clock-less conditions by characterization of the FGF/extracellular signal-regulated kinase (ERK) activity dynamics. Since features of the molecular clock have already been described in-depth in several reviews, we summarized recent findings regarding the role of FGF/ERK signaling in Somite boundary formation and described our current understanding of how FGF/ERK signaling contributes to somitogenesis in normal and clock-less conditions in this review.
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Somite reproducibility and stepwise ERK activity shift for Somite formation.
2019Co-Authors: Honda Naoki, Shin Ishii, Ryutaro Akiyama, Yasumasa Bessho, Dini Wahyu Kartika Sari, Takaaki MatsuiAbstract:(A) Lateral view of a wild-type zebrafish embryo during somitogenesis. (B, C) Somite morphology in wild-type (B) or clock-deficient embryos co-injected with her1 and her7 morpholinos. Nuclei are stained by propidium iodide (red). Somites are outlined by dotted lines. Scale bar: 100 μm. (D) Somite sizes in control and clock-deficient embryos (n = 16 each). The Somite size variation in clock-deficient embryos (61.1 ± 16.9 μm; C.V. = 0.28) was larger than that in control embryos (50.3 ± 3.6 μm; C.V. = 0.07). Data represent the means and standard deviations. (E) Representative dorsal view of PSM fgf8a mRNA expression at 3- to 5-Somite stages. Red line, fgf8a gradient boundary. Scale bars: 100 μm. (F) Quantitative presentation of fgf8a expression. Embryos (n = 29) were arranged in order of developmental stages, as estimated by Somite number and PSM length. High (purple stripe) and low (yellow stripe) fgf8a expression domains in each embryo. (G) Representative dorsal view of PSM pERK distribution at 3- to 5-Somite stages. Red line, pERK boundary. (H) Quantitative presentation of pERK distribution. Embryos (n = 39) were arranged as in (F). ON (red stripe) and OFF (blue stripe) ERK activity regions in each embryo. Panels B, C, and E-H are adapted with permission from our previous paper [5].
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Removing ERK signaling positive feedback erases robustness against noise.
2019Co-Authors: Honda Naoki, Shin Ishii, Ryutaro Akiyama, Yasumasa Bessho, Dini Wahyu Kartika Sari, Takaaki MatsuiAbstract:(A) Simulation settings. Simulations were performed with a 5-fold increase in noise variance upon positive feedback removal (i.e., w = 1.5, a = 0 in Eq 2). (B) Without positive feedback, PSM ERK activity was monotonically distributed (black line). Green line, FGF gradient. (C) Somites are regular in the absence of noise (50.0 ± 0 μm; C.V. = 0). (D) In the presence of noise, Somites become irregular (34.4 ± 12.0 μm; C.V. = 0.35) compared to the same conditions with positive feedback (50.0 ± 5.2 μm; C.V. = 0.10). This result suggests that positive feedback-induced bistability is necessary for Somite reproducibility subject to noise.
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Stepwise ERK activity shift without the clock.
2019Co-Authors: Honda Naoki, Shin Ishii, Ryutaro Akiyama, Yasumasa Bessho, Dini Wahyu Kartika Sari, Takaaki MatsuiAbstract:(A) Simulation settings. Simulations were performed upon clock removal (i.e., d = 0 in Eq 2). (B-C) Representative simulation results minus the segmentation clock with noise ×1 (B) and ×2 (C) (D) Noise effect on Somite size without the clock. The formation of 200 Somites was simulated by changing the noise variance from 0 to 10-fold. Data represent the means and standard deviations. (E-G) Representative simulation results without both clock and noise (E), without both clock and cell-cell interactions (26.2 ± 6.5 μm; C.V. = 0.24), (F) and without both clock and bistability (38.5 ± 19.2 μm; C.V. = 0.50) (G). Neither the stepwise ERK activity shift nor regular Somite patterning occurred under these conditions.
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an anterior limit of fgf erk signal activity marks the earliest future Somite boundary in zebrafish
Development, 2014Co-Authors: Ryutaro Akiyama, Miwa Masuda, Shoichiro Tsuge, Yasumasa Bessho, Takaaki MatsuiAbstract:Vertebrate segments called Somites are generated by periodic segmentation of the anterior extremity of the presomitic mesoderm (PSM). During Somite segmentation in zebrafish, mesp-b determines a future Somite boundary at position B-2 within the PSM. Heat-shock experiments, however, suggest that an earlier future Somite boundary exists at B-5, but the molecular signature of this boundary remains unidentified. Here, we characterized fibroblast growth factor (FGF) signal activity within the PSM, and demonstrated that an anterior limit of downstream Erk activity corresponds to the future B-5 Somite boundary. Moreover, the segmentation clock is required for a stepwise posterior shift of the Erk activity boundary during each segmentation. Our results provide the first molecular evidence of the future Somite boundary at B-5, and we propose that clock-dependent cyclic inhibition of the FGF/Erk signal is a key mechanism in the generation of perfect repetitive structures in zebrafish development.
Olivier Pourquié - One of the best experts on this subject based on the ideXlab platform.
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paraxial mesoderm organoids model development of human Somites
bioRxiv, 2021Co-Authors: Christoph Budjan, Olivier Pourquié, Sophia Liu, Adrian Ranga, S Gayen, Sahand HormozAbstract:Abstract During the development of the vertebrate embryo, segmented structures called Somites are periodically formed from the presomitic mesoderm (PSM), and give rise to the vertebral column. While Somite formation has been studied in several animal models, it is less clear how well this process is conserved in humans. Recent progress has made it possible to study aspects of human paraxial mesoderm development such as the human segmentation clock in vitro using human pluripotent stem cells (hPSCs), however, Somite formation has not been observed in these monolayer cultures. Here, we describe the generation of human paraxial mesoderm (PM) organoids from hPSCs (termed Somitoids), which recapitulate the molecular, morphological and functional features of paraxial mesoderm development, including formation of Somite-like structures in vitro. Using a quantitative image-based screen, we identify critical parameters such as initial cell number and signaling modulations that reproducibly yielded Somite formation in our organoid system. In addition, using single-cell RNA sequencing and 3D imaging, we show that PM organoids both transcriptionally and morphologically resemble their in vivo counterparts and can be differentiated into Somite derivatives. Our organoid system is reproducible and scalable, allowing for the systematic and quantitative analysis of human spinal cord development and disease in vitro.
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Somite formation in the chicken embryo
The International Journal of Developmental Biology, 2018Co-Authors: Olivier PourquiéAbstract: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 17th 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.
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papc couples the segmentation clock to Somite morphogenesis by regulating n cadherin dependent adhesion
Development, 2017Co-Authors: Jerome Chal, Charlene Guillot, Olivier PourquiéAbstract:Vertebrate segmentation is characterized by the periodic formation of epithelial Somites from the mesenchymal presomitic mesoderm (PSM). How the rhythmic signaling pulse delivered by the segmentation clock is translated into the periodic morphogenesis of Somites remains poorly understood. Here, we focused on the role of paraxial protocadherin (PAPC/Pcdh8) in this process. We showed that in chicken and mouse embryos, PAPC expression is tightly regulated by the clock and wavefront system in the posterior PSM. We observed that PAPC exhibits a striking complementary pattern to N-cadherin (CDH2), marking the interface of the future Somite boundary in the anterior PSM. Gain and loss of function of PAPC in chicken embryos disrupted Somite segmentation by altering the CDH2-dependent epithelialization of PSM cells. Our data suggest that clathrin-mediated endocytosis is increased in PAPC-expressing cells, subsequently affecting CDH2 internalization in the anterior compartment of the future Somite. This in turn generates a differential adhesion interface, allowing formation of the acellular fissure that defines the Somite boundary. Thus, periodic expression of PAPC in the anterior PSM triggers rhythmic endocytosis of CDH2, allowing for segmental de-adhesion and individualization of Somites.
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the segmentation clock converting embryonic time into spatial pattern
Science, 2003Co-Authors: Olivier PourquiéAbstract:In most animal species, the anteroposterior body axis is generated by the formation of repeated structures called segments. In vertebrate segmentation, a specialized mesodermal structure called the Somite gives rise to skeletal muscles, vertebrae, and some dermis. Formation of the Somites is a rhythmic process that involves an oscillator—the segmentation clock— driven by Wnt and Notch signaling. The clock ticks in Somite precursors and halts when they reach a specific maturation stage defined as the wavefront, established by fibroblast growth factor and Wnt signaling. This process converts the temporal oscillations into the periodic spatial pattern of Somite boundaries. The study of Somite development provides insights into the spatiotemporal integration of signaling systems in the vertebrate embryo.
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A molecular clock involved in Somite segmentation
Current topics in developmental biology, 2001Co-Authors: Miguel Maroto, Olivier PourquiéAbstract:Somites are transient embryonic structures that are formed from the unsegmented presomitic mesoderm (PSM) in a highly regulated process called somitogenesis. Somite, formation can be considered as the result of several sequential processes: generation of a basic metameric pattern, specification of the antero-posterior identity of each Somite, and, finally, formation of the somitic border. Evidence for the existence of a molecular clock or oscillator linked to somitogenesis has been provided by the discovery of the rhythmic and dynamic expression in the PSM of c-hairyl and lunatic fringe, two genes potentially related to the Notch signaling pathway. These oscillating expression patterns suggest that an important role of the molecular clock could reside in the temporal control of periodic Notch activation, ultimately resulting in the regular array of the Somites. We discuss both the importance of the Notch signaling pathway in the molecular events of somitogenesis and its relationship with the molecular clock, and, finally, in that context we review a number of other genes known to play a role in somitogenesis.
Charles P Emerson - One of the best experts on this subject based on the ideXlab platform.
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gli2 and gli3 have redundant and context dependent function in skeletal muscle formation
Development, 2005Co-Authors: Aileen Mcdermott, Charles P Emerson, Chichung Hui, Marcus K Gustafsson, Thomas Elsam, Anne-gaëlle BoryckiAbstract:The Gli family of zinc finger transcription factors are mediators of Shh signalling in vertebrates. In previous studies, we showed that Shh signalling, via an essential Gli -binding site in the Myf5 epaxial Somite (ES) enhancer, is required for the specification of epaxial muscle progenitor cells. Shh signalling is also required for the normal mediolateral patterning of myogenic cells within the Somite. In this study, we investigate the role and the transcriptional activities of Gli proteins during Somite myogenesis in the mouse embryo. We report that Gli genes are differentially expressed in the mouse Somite. Gli2 and Gli3 are essential for Gli1 expression in Somites, establishing Gli2 and Gli3 as primary mediators and Gli1 as a secondary mediator of Shh signalling. Combining genetic studies with the use of a transgenic mouse line expressing a reporter gene under the control of the Myf5 epaxial Somite enhancer, we show that Gli2 or Gli3 is required for Myf5 activation in the epaxial muscle progenitor cells. Furthermore, Gli3, but not Gli2 represses Myf5 transcription in a dose-dependent manner in the absence of Shh. Finally, we provide evidence that hypaxial and myotomal gene expression is mispatterned in Gli2–/–Gli3–/– and Gli3–/–Shh–/– Somites. Together, our data demonstrate both positive and negative regulatory functions for Gli2 and Gli3 in the control of Myf5 activation in the epaxial muscle progenitor cells and in dorsoventral and mediolateral patterning of the Somite.
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control of Somite patterning by sonic hedgehog and its downstream signal response genes
Development, 1998Co-Authors: Anne-gaëlle Borycki, L Mendham, Charles P EmersonAbstract:In the avian embryo, previous work has demonstrated that the notochord provides inductive signals to activate myoD and pax1 regulatory genes, which are expressed in the dorsal and ventral Somite cells that give rise to myotomal and sclerotomal lineages. Here, we present bead implantation and antisense inhibition experiments that show that Sonic hedgehog is both a sufficient and essential notochord signal molecule for myoD and pax1 activation in Somites. Furthermore, we show that genes of the Sonic hedgehog signal response pathway, specifically patched, the Sonic hedgehog receptor, and gli and gli2/4, zinc-finger transcription factors, are activated in coordination with Somite formation, establishing that Sonic hedgehog response genes play a regulatory role in coordinating the response of Somites to the constitutive notochord Sonic hedgehog signal. Furthermore, the expression of patched, gli and gli2/4 is differentially patterned in the Somite, providing mechanisms for differentially transducing the Sonic hedgehog signal to the myotomal and sclerotomal lineages. Finally, we show that the activation of gli2/4 is controlled by the process of Somite formation and signals from the surface ectoderm, whereas upregulation of patched and activation of gli is controlled by the process of Somite formation and a Sonic hedgehog signal. The Sonic hedgehog signal response genes, therefore, have important functions in regulating the initiation of the Sonic hedgehog response in newly forming Somites and in regulating the patterned expression of myoD and pax1 in the myotomal and sclerotomal lineages following Somite formation.
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sequential activation of three myogenic regulatory genes during Somite morphogenesis in quail embryos
Developmental Biology, 1992Co-Authors: Mary Elizabeth Pownall, Charles P EmersonAbstract:We report the cloning of two new quail myogenic cDNAs, quail myogenic factor 2 (qmf2) and qmf3, which encode helix-loop-helix proteins homologous to mammalian myogenic factors myogenin and myf-5. In situ hybridization has been used to investigate the developmental expression of qmf2 and qmf3, as well as qmf1, the quail homologue to mammalian MyoD1, during the formation of the brachial Somites. These studies show that qmf1 and qmf3 are activated sequentially in medially localized Somite cells, immediately following Somite formation but prior to myotome formation. qmf1, qmf2, and qmf3 are expressed in the myotome of compartmentalized Somites. These findings suggest that determination of the myogenic cell lineage in quail Somites is a progressive process controlled by influences of the neural tube on the expression of the qmf regulatory genes in newly forming Somites.
Andrea Münsterberg - One of the best experts on this subject based on the ideXlab platform.
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4d imaging reveals stage dependent random and directed cell motion during Somite morphogenesis
Scientific Reports, 2018Co-Authors: James Mccoll, Gi Fay Mok, Anna Lippert, Aleks Ponjavic, Leila Muresan, Andrea MünsterbergAbstract:Somites are paired embryonic segments that form in a regular sequence from unsegmented mesoderm during vertebrate development. Although transient structures they are of fundamental importance as they generate cell lineages of the musculoskeletal system in the trunk such as cartilage, tendon, bone, endothelial cells and skeletal muscle. Surprisingly, very little is known about cellular dynamics underlying the morphological transitions during Somite differentiation. Here, we address this by examining cellular rearrangements and morphogenesis in differentiating Somites using live multi-photon imaging of transgenic chick embryos, where all cells express a membrane-bound GFP. We specifically focussed on the dynamic cellular changes in two principle regions within the Somite, the medial and lateral domains, to investigate extensive morphological transformations. Furthermore, by using quantitative analysis and cell tracking, we capture for the first time a directed movement of dermomyotomal progenitor cells towards the rostro-medial domain of the dermomyotome, where skeletal muscle formation initiates.
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4d imaging reveals stage dependent random and directed cell motion during Somite morphogenesis
bioRxiv, 2018Co-Authors: James Mccoll, Gi Fay Mok, Anna Lippert, Aleks Ponjavic, Leila Muresan, Andrea MünsterbergAbstract:Somites are paired embryonic segments that form in a regular sequence from unsegmented mesoderm during vertebrate development. Of fundamental importance, they are transient structures that generate cell lineages of the musculoskeletal system in the trunk such as cartilage, tendon, bone, endothelial cells and skeletal muscle. Surprisingly, very little is known about the morphological transition and cellular dynamics during Somite differentiation. Here, we address this by examining cellular rearrangements and morphogenesis in differentiating Somites using live multi photon imaging of GFP-transgenic chick embryos. We specifically focussed on the dynamic changes in two principle regions within the Somite (the medial and lateral domains) to investigate extensive morphological changes. Furthermore, by using quantitative analysis and cell tracking, we were able to capture for the first time a progenitor cell bulk movement towards the rostral-medial domain of the myotome, where skeletal muscle formation first initiates.
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Combinatorial signals from the neural tube, floor plate and notochord induce myogenic bHLH gene expression in the Somite
Development (Cambridge England), 1995Co-Authors: Andrea Münsterberg, Andrew B. LassarAbstract:The neural tube, floor plate and notochord are axial tissues in the vertebrate embryo which have been demonstrated to play a role in Somite morphogenesis. Using in vitro coculture of tissue explants, we have monitored inductive interactions of these axial tissues with the adjacent somitic mesoderm in chick embryos. We have found that signals from the neural tube and floor plate/notochord are necessary for expression of the myogenic bHLH regulators MyoD, Myf5 and myogenin in the Somite. Eventually somitic expression of the myogenic bHLH genes is maintained in the absence of the axial tissues. In organ culture, at early developmental stages (HH 11-), induction of myogenesis in the three most recently formed Somites can be mediated by the neural tube together with the floor plate/notochord, while in more rostral Somites (stages IV-IX) the neural tube without the floor plate/notochord is sufficient. By recombining Somites and neural tubes from different axial levels of the embryo, we have found that a second signal is necessary to promote competence of the Somite to respond to inducing signals from the neural tube. Thus, we propose that at least two signals from axial tissues work in combination to induce myogenic bHLH gene expression; one signal derives from the floor plate/notochord and the other signal derives from regions of the neural tube other than the floor plate.
Randy L. Johnson - One of the best experts on this subject based on the ideXlab platform.
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dynamic expression of lunatic fringe suggests a link between notch signaling and an autonomous cellular oscillator driving Somite segmentation
Developmental Biology, 1999Co-Authors: Alexander Aulehla, Randy L. JohnsonAbstract:The metameric organization of the vertebrate trunk is a characteristic feature of all members of this phylum. The origin of this metamerism can be traced to the division of paraxial mesoderm into individual units, termed Somites, during embryonic development. Despite the identification of Somites as the first overt sign of segmentation in vertebrates well over 100 years ago, the mechanism(s) underlying Somite formation remain poorly understood. Recently, however, several genes have been identified which play prominent roles in orchestrating segmentation, including the novel secreted factor lunatic fringe. To gain further insight into the mechanism by which lunatic fringe controls Somite development, we have conducted a thorough analysis of lunatic fringe expression in the unsegmented paraxial mesoderm of chick embryos. Here we report that lunatic fringe is expressed predominantly in Somite -II, where Somite I corresponds to the most recently formed Somite and Somite -I corresponds to the group of cells which will form the next Somite. In addition, we show that lunatic fringe is expressed in a highly dynamic manner in the chick segmental plate prior to Somite formation and that lunatic fringe expression cycles autonomously with a periodicity of Somite formation. Moreover, the murine ortholog of lunatic fringe undergoes a similar cycling expression pattern in the presomitic mesoderm of Somite stage mouse embryos. The demonstration of a dynamic periodic expression pattern suggests that lunatic fringe may function to integrate notch signaling to a cellular oscillator controlling Somite segmentation.
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Ectopic expression of Sonic hedgehog alters dorsal-ventral patterning of Somites
Cell, 1994Co-Authors: Randy L. Johnson, Ed Laufer, Robert D RiddleAbstract:Abstract Differentiation of Somites into sclerotome, dermatome, and myotome is controlled by a complex set of inductive interactions. The ability of axial midline tissues, the notochord and floor plate, to induce sclerotome has been well documented and has led to models in which ventral Somite identity is specified by signals derived from the notochord and floor plate. Herein, we provide evidence that Sonic hedgehog , a vertebrate homolog of the Drosophila segment polarity gene hedgehog , is a signal produced by the notochord and floor plate that directs ventral Somite differentiation. Sonic hedgehog is expressed in ventral midline tissues at critical times during Somite specification and has the ability, when ectopically expressed, to enhance the formation of sclerotome and antagonize the development of dermatome.
