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Eldad Tzahor - One of the best experts on this subject based on the ideXlab platform.
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Craniofacial Muscle Development.
Current topics in developmental biology, 2015Co-Authors: Inbal Michailovici, Tamar Eigler, Eldad TzahorAbstract:The developmental mechanisms that control Head Muscle formation are distinct from those that operate in the trunk. Head and neck Muscles derive from various mesoderm populations in the embryo and are regulated by distinct transcription factors and signaling molecules. Throughout the last decade, developmental, and lineage studies in vertebrates and invertebrates have revealed the peculiar nature of the pharyngeal mesoderm that forms certain Head Muscles and parts of the heart. Studies in chordates, the ancestors of vertebrates, revealed an evolutionarily conserved cardiopharyngeal field that progressively facilitates the development of both heart and craniofacial structures during vertebrate evolution. This ancient regulatory circuitry preceded and facilitated the emergence of myogenic cell types and hierarchies that exist in vertebrates. This chapter summarizes studies related to the origins, signaling circuits, genetics, and evolution of the Head musculature, highlighting its heterogeneous characteristics in all these aspects, with a special focus on the FGF-ERK pathway. Additionally, we address the processes of Head Muscle regeneration, and the development of stem cell-based therapies for treatment of Muscle disorders.
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Head Muscle Development
Results and problems in cell differentiation, 2014Co-Authors: Eldad TzahorAbstract:The developmental paths that lead to the formation of skeletal Muscles in the Head are distinct from those operating in the trunk. Craniofacial Muscles are associated with Head and neck structures. In the embryo, these structures derive from distinct mesoderm populations. Distinct genetic programs regulate different groups of Muscles within the Head to generate diverse Muscle specifications. Developmental and lineage studies in vertebrates and invertebrates demonstrated an overlap in progenitor populations derived from the pharyngeal mesoderm that contribute to certain Head Muscles and the heart. These studies reveal that the genetic program controlling pharyngeal Muscles overlaps with that of the heart. Indeed cardiac and craniofacial birth defects are often linked. Recent studies suggest that early chordates, the last common ancestor of tunicates and vertebrates, had an ancestral pharyngeal mesoderm lineage that later during evolution gave rise to both heart and craniofacial structures. This chapter summarizes studies related to the origins, signaling, genetics, and evolution of the Head musculature, highlighting its heterogeneous characteristics in all these aspects.
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The occipital lateral plate mesoderm is a novel source for vertebrate neck musculature
Development (Cambridge England), 2010Co-Authors: Susanne Theis, Eldad Tzahor, Itamar Harel, Shahragim Tajbakhsh, Ketan Patel, Petr Valasek, Anthony Otto, Bodo Christ, Ruijin HuangAbstract:In vertebrates, body musculature originates from somites, whereas Head Muscles originate from the cranial mesoderm. Neck Muscles are located in the transition between these regions. We show that the chick occipital lateral plate mesoderm has myogenic capacity and gives rise to large Muscles located in the neck and thorax. We present molecular and genetic evidence to show that these Muscles not only have a unique origin, but additionally display a distinct temporal development, forming later than any other Muscle group described to date. We further report that these Muscles, found in the body of the animal, develop like Head musculature rather than deploying the programme used by the trunk Muscles. Using mouse genetics we reveal that these Muscles are formed in trunk Muscle mutants but are absent in Head Muscle mutants. In concordance with this conclusion, their connective tissue is neural crest in origin. Finally, we provide evidence that the mechanism by which these neck Muscles develop is conserved in vertebrates.
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Heart and craniofacial Muscle development: a new developmental theme of distinct myogenic fields.
Developmental biology, 2009Co-Authors: Eldad TzahorAbstract:Head Muscle development has been studied less intensively than myogenesis in the trunk, although this situation is gradually changing, as embryological and genetic insights accumulate. This review focuses on novel studies of the origins, composition and evolution of distinct craniofacial Muscles. Cellular and molecular parallels are drawn between cardiac and branchiomeric Muscle developmental programs, both of which utilize multiple lineages with distinct developmental histories, and argue for the tissues' common evolutionary origin. In addition, there is increasing evidence that the specification of skeletal Muscles in the Head appears to be distinct from that operating in the trunk: considerable variation among the different craniofacial Muscle groups is seen, in a manner resembling myogenic specification in lower organisms.
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Distinct origins and genetic programs of Head Muscle satellite cells.
Developmental cell, 2009Co-Authors: Itamar Harel, Elisha Nathan, Libbat Tirosh-finkel, Hila Zigdon, Nuno Guimarães-camboa, Sylvia M. Evans, Eldad TzahorAbstract:Adult skeletal Muscle possesses a remarkable regenerative capacity, due to the presence of satellite cells, adult Muscle stem cells. We used fate-mapping techniques in avian and mouse models to show that trunk (Pax3(+)) and cranial (MesP1(+)) skeletal Muscle and satellite cells derive from separate genetic lineages. Similar lineage heterogeneity is seen within the Head musculature and satellite cells, due to their shared, heterogenic embryonic origins. Lineage tracing experiments with Isl1Cre mice demonstrated the robust contribution of Isl1(+) cells to distinct jaw Muscle-derived satellite cells. Transplantation of myofiber-associated, Isl1-derived satellite cells into damaged limb Muscle contributed to Muscle regeneration. In vitro experiments demonstrated the cardiogenic nature of cranial- but not trunk-derived satellite cells. Finally, overexpression of Isl1 in the branchiomeric Muscles of chick embryos inhibited skeletal Muscle differentiation in vitro and in vivo, suggesting that this gene plays a role in the specification of cardiovascular and skeletal Muscle stem cell progenitors.
Lionel Christiaen - One of the best experts on this subject based on the ideXlab platform.
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A single-cell transcriptional roadmap for cardiopharyngeal fate diversification
Nature cell biology, 2019Co-Authors: Wei Wang, Robert G. Kelly, Xiang Niu, Tim Stuart, Estelle Jullian, William M. Mauck, Rahul Satija, Lionel ChristiaenAbstract:In vertebrates, multipotent progenitors located in the pharyngeal mesoderm form cardiomyocytes and branchiomeric Head Muscles, but the dynamic gene expression programmes and mechanisms underlying cardiopharyngeal multipotency and heart versus Head Muscle fate choices remain elusive. Here, we used single-cell genomics in the simple chordate model Ciona to reconstruct developmental trajectories forming first and second heart lineages and pharyngeal Muscle precursors and characterize the molecular underpinnings of cardiopharyngeal fate choices. We show that FGF–MAPK signalling maintains multipotency and promotes the pharyngeal Muscle fate, whereas signal termination permits the deployment of a pan-cardiac programme, shared by the first and second heart lineages, to define heart identity. In the second heart lineage, a Tbx1/10-Dach pathway actively suppresses the first heart lineage programme, conditioning later cell diversity in the beating heart. Finally, cross-species comparisons between Ciona and the mouse evoke the deep evolutionary origins of cardiopharyngeal networks in chordates. Wang et al. map early cardiopharyngeal development in the chordate model Ciona and show that FGF–MAPK signalling maintains multipotency and promotes pharyngeal Muscle fate, whereas Tbx1/10-Dach specify second heart lineage identity.
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Initial characterization of Wnt-Tcf functions during Ciona heart development.
Developmental biology, 2019Co-Authors: Nicole Kaplan, Wei Wang, Lionel ChristiaenAbstract:In vertebrate embryos, the cardiopharyngeal mesoderm gives rise to both cardiac and branchiomeric Head Muscles. The canonical Wnt signaling pathway regulates many aspects of cardiomyocyte specification, and modulates a balance between skeletal and cardiac myogenesis during vertebrate Head Muscle development. However, the role of Wnt signaling during ascidian cardiopharyngeal development remains elusive. Here, we documented the expression of Wnt pathway components during cardiopharyngeal development in Ciona, and generated tools to investigate potential roles for Wnt signaling, and its transcriptional effector Tcf, on heart vs. pharyngeal Muscle fate specification. Neither focused functional analyses nor lineage-specific transcriptome profiling uncovered a significant role for Tcf during early cardiac vs. pharyngeal Muscle fate choice. By contrast, Wnt gene expression patterns of Frizzled4 and Lrp4/8 and CRISPR/Cas9-mediated Tcf knock-down suggested a later requirement for Wnt signaling during heart morphogenesis and/or cardiomyocyte differentiation. This study provides a provisional set of reagents to study Wnt signaling function in Ciona, and promising insights for future analyses of Wnt functions during heart organogenesis.
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A single cell transcriptional roadmap for cardiopharyngeal fate diversification
2017Co-Authors: Wei Wang, Robert G. Kelly, Xiang Niu, Estelle Jullian, Rahul Satija, Lionel ChristiaenAbstract:Dynamic gene expression programs determine multipotent cell states and fate choices during development. Multipotent progenitors for cardiomyocytes and branchiomeric Head Muscles populate the pharyngeal mesoderm of vertebrate embryos, but the mechanisms underlying cardiopharyngeal multipotency and heart vs. Head Muscle fate choices remain elusive. The tunicate Ciona emerged as a simple chordate model to study cardiopharyngeal development with unprecedented spatio-temporal resolution. We analyzed the transcriptome of single cardiopharyngeal lineage cells isolated at successive time points encompassing the transitions from multipotent progenitors to distinct first and second heart, and pharyngeal Muscle precursors. We reconstructed the three cardiopharyngeal developmental trajectories, and characterized gene expression dynamics and regulatory states underlying each fate choice. Experimental perturbations and bulk transcriptome analyses revealed that ongoing FGF/MAPK signaling maintains cardiopharyngeal multipotency and promotes the pharyngeal Muscle fate, whereas signal termination permits the deployment of a full pan-cardiac program and heart fate specification. We identified the Dach1/2 homolog as a novel evolutionarily conserved second-heart-field-specific factor and demonstrate, through lineage tracing and CRISPR/Cas9 perturbations, that it operates downstream of Tbx1/10 to actively suppress the first heart lineage program. This data indicates that the regulatory state of multipotent cardiopharyngeal progenitors determines the first vs. second heart lineage choice, and that Tbx1/10 acts as a bona fide regulator of cardiopharyngeal multipotency.
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The chordate origins of the second heart field and Head Muscle stem cells (345.2)
The FASEB Journal, 2014Co-Authors: Lionel ChristiaenAbstract:The vertebrate Head and cardiac Muscles share a common origin in the pharyngeal mesoderm, but the cellular and molecular details of the initial fate choices remain obscured by the complexity of vertebrate embryos. In ascidians, common progenitors of heart and atrial siphon Muscle (ASM) undergo stereotyped asymmetric divisions to produce first heart precursors, second heart precursors and ASM precursors. The ASM-specific transcription factor COE is necessary and sufficient to promote pharyngeal Muscle specification and block the heart program. We found that a cross-antagonism between Tbx1 and NK4/Nkx2-5 activities acts upstream of COE and GATAa to direct pharyngeal Muscle versus heart specification in separate ASM and second heart precursors, respectively. Using a genomics approach, we showed both the cardiac and pharyngeal Muscle programs are primed in cardiopharyngeal progenitors. We show that, following fate restriction, ASM precursors produce the myofibers that differentiate, and Notch-mediated lateral...
Robert G. Kelly - One of the best experts on this subject based on the ideXlab platform.
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A single-cell transcriptional roadmap for cardiopharyngeal fate diversification
Nature cell biology, 2019Co-Authors: Wei Wang, Robert G. Kelly, Xiang Niu, Tim Stuart, Estelle Jullian, William M. Mauck, Rahul Satija, Lionel ChristiaenAbstract:In vertebrates, multipotent progenitors located in the pharyngeal mesoderm form cardiomyocytes and branchiomeric Head Muscles, but the dynamic gene expression programmes and mechanisms underlying cardiopharyngeal multipotency and heart versus Head Muscle fate choices remain elusive. Here, we used single-cell genomics in the simple chordate model Ciona to reconstruct developmental trajectories forming first and second heart lineages and pharyngeal Muscle precursors and characterize the molecular underpinnings of cardiopharyngeal fate choices. We show that FGF–MAPK signalling maintains multipotency and promotes the pharyngeal Muscle fate, whereas signal termination permits the deployment of a pan-cardiac programme, shared by the first and second heart lineages, to define heart identity. In the second heart lineage, a Tbx1/10-Dach pathway actively suppresses the first heart lineage programme, conditioning later cell diversity in the beating heart. Finally, cross-species comparisons between Ciona and the mouse evoke the deep evolutionary origins of cardiopharyngeal networks in chordates. Wang et al. map early cardiopharyngeal development in the chordate model Ciona and show that FGF–MAPK signalling maintains multipotency and promotes pharyngeal Muscle fate, whereas Tbx1/10-Dach specify second heart lineage identity.
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A single cell transcriptional roadmap for cardiopharyngeal fate diversification
2017Co-Authors: Wei Wang, Robert G. Kelly, Xiang Niu, Estelle Jullian, Rahul Satija, Lionel ChristiaenAbstract:Dynamic gene expression programs determine multipotent cell states and fate choices during development. Multipotent progenitors for cardiomyocytes and branchiomeric Head Muscles populate the pharyngeal mesoderm of vertebrate embryos, but the mechanisms underlying cardiopharyngeal multipotency and heart vs. Head Muscle fate choices remain elusive. The tunicate Ciona emerged as a simple chordate model to study cardiopharyngeal development with unprecedented spatio-temporal resolution. We analyzed the transcriptome of single cardiopharyngeal lineage cells isolated at successive time points encompassing the transitions from multipotent progenitors to distinct first and second heart, and pharyngeal Muscle precursors. We reconstructed the three cardiopharyngeal developmental trajectories, and characterized gene expression dynamics and regulatory states underlying each fate choice. Experimental perturbations and bulk transcriptome analyses revealed that ongoing FGF/MAPK signaling maintains cardiopharyngeal multipotency and promotes the pharyngeal Muscle fate, whereas signal termination permits the deployment of a full pan-cardiac program and heart fate specification. We identified the Dach1/2 homolog as a novel evolutionarily conserved second-heart-field-specific factor and demonstrate, through lineage tracing and CRISPR/Cas9 perturbations, that it operates downstream of Tbx1/10 to actively suppress the first heart lineage program. This data indicates that the regulatory state of multipotent cardiopharyngeal progenitors determines the first vs. second heart lineage choice, and that Tbx1/10 acts as a bona fide regulator of cardiopharyngeal multipotency.
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Clonal analysis reveals common lineage relationships between Head Muscles and second heart field derivatives in the mouse embryo
Development (Cambridge England), 2010Co-Authors: Fabienne Lescroart, Robert G. Kelly, Jean-françois Le Garrec, Jean-françois Nicolas, Sigolène M. Meilhac, Margaret BuckinghamAbstract:Head Muscle progenitors in pharyngeal mesoderm are present in close proximity to cells of the second heart field and show overlapping patterns of gene expression. However, it is not clear whether a single progenitor cell gives rise to both heart and Head Muscles. We now show that this is the case, using a retrospective clonal analysis in which an nlaacZ sequence, converted to functional nlacZ after a rare intragenic recombination event, is targeted to the αc-actin gene, expressed in all developing skeletal and cardiac Muscle. We distinguish two branchiomeric Head Muscle lineages, which segregate early, both of which also contribute to myocardium. The first gives rise to the temporalis and masseter Muscles, which derive from the first branchial arch, and also to the extraocular Muscles, thus demonstrating a contribution from paraxial as well as prechordal mesoderm to this anterior Muscle group. Unexpectedly, this first lineage also contributes to myocardium of the right ventricle. The second lineage gives rise to Muscles of facial expression, which derive from mesoderm of the second branchial arch. It also contributes to outflow tract myocardium at the base of the arteries. Further sublineages distinguish myocardium at the base of the aorta or pulmonary trunk, with a clonal relationship to right or left Head Muscles, respectively. We thus establish a lineage tree, which we correlate with genetic regulation, and demonstrate a clonal relationship linking groups of Head Muscles to different parts of the heart, reflecting the posterior movement of the arterial pole during pharyngeal morphogenesis.
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Relationship between Neural Crest Cells and Cranial Mesoderm during Head Muscle Development
PLoS ONE, 2009Co-Authors: Julien Grenier, Raphaëlle Grifone, Robert G. Kelly, Marie-aimée Teillet, Delphine DuprezAbstract:Background: In vertebrates, the skeletal elements of the jaw, together with the connective tissues and tendons, originate from neural crest cells, while the associated Muscles derive mainly from cranial mesoderm. Previous studies have shown that neural crest cells migrate in close association with cranial mesoderm and then circumscribe but do not penetrate the core of Muscle precursor cells of the branchial arches at early stages of development, thus defining a sharp boundary between neural crest cells and mesodermal Muscle progenitor cells. Tendons constitute one of the neural crest derivatives likely to interact with Muscle formation. However, Head tendon formation has not been studied, nor have tendon and Muscle interactions in the Head. Methodology/Principal Findings: Reinvestigation of the relationship between cranial neural crest cells and Muscle precursor cells during development of the first branchial arch, using quail/chick chimeras and molecular markers revealed several novel features concerning the interface between neural crest cells and mesoderm. We observed that neural crest cells migrate into the cephalic mesoderm containing myogenic precursor cells, leading to the presence of neural crest cells inside the mesodermal core of the first branchial arch. We have also established that all the forming tendons associated with branchiomeric and eye Muscles are of neural crest origin and express the Scleraxis marker in chick and mouse embryos. Moreover, analysis of Scleraxis expression in the absence of branchiomeric Muscles in Tbx1 2/2 mutant mice, showed that Muscles are not necessary for the initiation of tendon formation but are required for further tendon development.
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Relationship between Neural Crest Cells and Cranial Mesoderm during Head Muscle Development
PloS one, 2009Co-Authors: Julien Grenier, Raphaëlle Grifone, Robert G. Kelly, Marie-aimée Teillet, Delphine DuprezAbstract:Background In vertebrates, the skeletal elements of the jaw, together with the connective tissues and tendons, originate from neural crest cells, while the associated Muscles derive mainly from cranial mesoderm. Previous studies have shown that neural crest cells migrate in close association with cranial mesoderm and then circumscribe but do not penetrate the core of Muscle precursor cells of the branchial arches at early stages of development, thus defining a sharp boundary between neural crest cells and mesodermal Muscle progenitor cells. Tendons constitute one of the neural crest derivatives likely to interact with Muscle formation. However, Head tendon formation has not been studied, nor have tendon and Muscle interactions in the Head. Methodology/Principal Findings Reinvestigation of the relationship between cranial neural crest cells and Muscle precursor cells during development of the first branchial arch, using quail/chick chimeras and molecular markers revealed several novel features concerning the interface between neural crest cells and mesoderm. We observed that neural crest cells migrate into the cephalic mesoderm containing myogenic precursor cells, leading to the presence of neural crest cells inside the mesodermal core of the first branchial arch. We have also established that all the forming tendons associated with branchiomeric and eye Muscles are of neural crest origin and express the Scleraxis marker in chick and mouse embryos. Moreover, analysis of Scleraxis expression in the absence of branchiomeric Muscles in Tbx1−/− mutant mice, showed that Muscles are not necessary for the initiation of tendon formation but are required for further tendon development. Conclusions/Significance This results show that neural crest cells and Muscle progenitor cells are more extensively mixed than previously believed during arch development. In addition, our results show that interactions between Muscles and tendons during craniofacial development are similar to those observed in the limb, despite the distinct embryological origin of these cell types in the Head.
Richard Stephenson - One of the best experts on this subject based on the ideXlab platform.
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design and validation of a computer based sleep scoring algorithm
Journal of Neuroscience Methods, 2004Co-Authors: Rhain P Louis, Richard StephensonAbstract:Abstract A computer-based sleep scoring algorithm was devised for the real time scoring of sleep–wake state in Wistar rats. Electroencephalogram (EEG) amplitude (μV rms ) was measured in the following frequency bands: delta ( δ ; 1.5–6 Hz), theta ( Θ ; 6–10 Hz), alpha ( α ; 10.5–15 Hz), beta ( β ; 22–30 Hz), and gamma ( γ ; 35–45 Hz). Electromyographic (EMG) signals (μV rms ) were recorded from the levator auris longus (neck) Muscle, as this yielded a significantly higher algorithm accuracy than the spinodeltoid (shoulder) or temporalis (Head) Muscle EMGs (ANOVA; P =0.009). Data were obtained using either tethers ( n =10) or telemetry ( n =4). We developed a simple three-step algorithm that categorizes behavioural state as wake, non-rapid eye movement (NREM) sleep, rapid eye movement (REM) sleep, based on thresholds set during a manually-scored 90-min preliminary recording. Behavioural state was assigned in 5-s epochs. EMG amplitude and ratios of EEG frequency band amplitudes were measured, and compared with empirical thresholds in each animal. STEP 1: EMG amplitude greater than threshold? Yes: “active” wake, no: sleep or “quiet” wake. STEP 2: EEG amplitude ratio ( δ × α )/( β × γ ) greater than threshold? Yes: NREM, no: REM or “quiet” wake. STEP 3: EEG amplitude ratio Θ 2 /( δ × α ) greater than threshold? Yes: REM, no: “quiet” wake. The algorithm was validated with one, two and three steps. The overall accuracy in discriminating wake and sleep (NREM and REM combined) using step one alone was found to be 90.1%. Overall accuracy using the first two steps was found to be 87.5% in scoring wake, NREM and REM sleep. When all three steps were used, overall accuracy in scoring wake, NREM and REM sleep was determined to be 87.9%. All accuracies were derived from comparisons with unequivocally-scored epochs from four 90-min recordings as defined by an experienced human rater. The algorithms were as reliable as the agreement between three human scorers (88%).
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Design and validation of a computer-based sleep-scoring algorithm.
Journal of neuroscience methods, 2004Co-Authors: Rhain P Louis, Richard StephensonAbstract:A computer-based sleep scoring algorithm was devised for the real time scoring of sleep-wake state in Wistar rats. Electroencephalogram (EEG) amplitude (microV(rms)) was measured in the following frequency bands: delta (delta; 1.5-6 Hz), theta (Theta; 6-10 Hz), alpha (alpha; 10.5-15 Hz), beta (beta; 22-30 Hz), and gamma (gamma; 35-45 Hz). Electromyographic (EMG) signals (microV(rms)) were recorded from the levator auris longus (neck) Muscle, as this yielded a significantly higher algorithm accuracy than the spinodeltoid (shoulder) or temporalis (Head) Muscle EMGs (ANOVA; P=0.009). Data were obtained using either tethers (n=10) or telemetry (n=4). We developed a simple three-step algorithm that categorizes behavioural state as wake, non-rapid eye movement (NREM) sleep, rapid eye movement (REM) sleep, based on thresholds set during a manually-scored 90-min preliminary recording. Behavioural state was assigned in 5-s epochs. EMG amplitude and ratios of EEG frequency band amplitudes were measured, and compared with empirical thresholds in each animal.STEP 1: EMG amplitude greater than threshold? Yes: "active" wake, no: sleep or "quiet" wake. STEP 2: EEG amplitude ratio (delta x alpha)/(beta x gamma) greater than threshold? Yes: NREM, no: REM or "quiet" wake. STEP 3: EEG amplitude ratio Theta(2)/(delta x alpha) greater than threshold? Yes: REM, no: "quiet" wake. The algorithm was validated with one, two and three steps. The overall accuracy in discriminating wake and sleep (NREM and REM combined) using step one alone was found to be 90.1%. Overall accuracy using the first two steps was found to be 87.5% in scoring wake, NREM and REM sleep. When all three steps were used, overall accuracy in scoring wake, NREM and REM sleep was determined to be 87.9%. All accuracies were derived from comparisons with unequivocally-scored epochs from four 90-min recordings as defined by an experienced human rater. The algorithms were as reliable as the agreement between three human scorers (88%).
Susanne Dietrich - One of the best experts on this subject based on the ideXlab platform.
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To roll the eyes and snap a bite - function, development and evolution of craniofacial Muscles.
Seminars in cell & developmental biology, 2018Co-Authors: Frank R. Schubert, Arun J. Singh, Oluwatomisin Afoyalan, Chrissa Kioussi, Susanne DietrichAbstract:Abstract Craniofacial Muscles, Muscles that move the eyes, control facial expression and allow food uptake and speech, have long been regarded as a variation on the general body Muscle scheme. However, evidence has accumulated that the function of Head Muscles, their developmental anatomy and the underlying regulatory cascades are distinct. This article reviews the key aspects of craniofacial Muscle and Muscle stem cell formation and discusses how this differs from the trunk programme of myogenesis; we show novel RNAseq data to support this notion. We also trace the origin of Head Muscle in the chordate ancestors of vertebrates and discuss links with smooth-type Muscle in the primitive chordate pharynx. We look out as to how the special properties of Head Muscle precursor and stem cells, in particular their competence to contribute to the heart, could be exploited in regenerative medicine.
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The emergence of Pax7-expressing Muscle stem cells during vertebrate Head Muscle development
Frontiers in aging neuroscience, 2015Co-Authors: Julia Meireles Nogueira, Katarzyna Hawrot, Colin Sharpe, Anna Noble, William M. Wood, Erika Cristina Jorge, David J. Goldhamer, Gabrielle Kardon, Susanne DietrichAbstract:Pax7 expressing Muscle stem cells accompany all skeletal Muscles in the body and in healthy individuals, efficiently repair Muscle after injury. Currently, the in vitro manipulation and culture of these cells is still in its infancy, yet Muscle stem cells may be the most promising route towards the therapy of Muscle diseases such as muscular dystrophies. It is often overlooked that muscular dystrophies affect Head and body skeletal Muscle differently. Moreover, these Muscles develop differently. Specifically, Head Muscle and its stem cells develop from the non-somitic Head mesoderm which also has cardiac competence. To which extent Head Muscle stem cells retain properties of the early Head mesoderm and might even be able to switch between a skeletal Muscle and cardiac fate is not known. This is due to the fact that the timing and mechanisms underlying Head Muscle stem cell development are still obscure. Consequently, it is not clear at which time point one should compare the properties of Head mesodermal cells and Head Muscle stem cells. To shed light on this, we traced the emergence of Head Muscle stem cells in the key vertebrate models for myogenesis, chicken, mouse, frog and zebrafish, using Pax7 as key marker. Our study reveals a common theme of Head Muscle stem cell development that is quite different from the trunk. Unlike trunk Muscle stem cells, Head Muscle stem cells do not have a previous history of Pax7 expression, instead Pax7 expression emerges de-novo. The cells develop late, and well after the Head mesoderm has committed to myogenesis. We propose that this unique mechanism of Muscle stem cell development is a legacy of the evolutionary history of the chordate Head mesoderm.
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Antagonists of Wnt and BMP signaling promote the formation of vertebrate Head Muscle
Genes & development, 2003Co-Authors: Eldad Tzahor, Susanne Dietrich, Hervé Kempf, Roy C. Mootoosamy, Andy C. Poon, Arkhat Abzhanov, Clifford J. Tabin, Andrew B. LassarAbstract:Recent studies have postulated that distinct regulatory cascades control myogenic differentiation in the Head and the trunk. However, although the tissues and signaling molecules that induce skeletal myogenesis in the trunk have been identified, the source of the signals that trigger skeletal Muscle formation in the Head remain obscure. Here we show that although myogenesis in the trunk paraxial mesoderm is induced by Wnt signals from the dorsal neural tube, myogenesis in the cranial paraxial mesoderm is blocked by these same signals. In addition, BMP family members that are expressed in both the dorsal neural tube and surface ectoderm are also potent inhibitors of myogenesis in the cranial paraxial mesoderm. We provide evidence suggesting that skeletal myogenesis in the Head is induced by the BMP inhibitors, Noggin and Gremlin, and the Wnt inhibitor, Frzb. These molecules are secreted by both cranial neural crest cells and by other tissues surrounding the cranial Muscle anlagen. Our findings demonstrate that Head Muscle formation is locally repressed by Wnt and BMP signals and induced by antagonists of these signaling pathways secreted by adjacent tissues.
