Anatomy articles within Nature Communications

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  • Article
    | Open Access

    Uncoupling of mature oocytes from somatic granulosa cells is required for their fertilization. Here the authors show that activation of EGFR signalling in granulosa cells during ovulation triggers ERK-dependent loss of filopodia oocyte adhesion, and Arp2/3 mediated retraction of granulosa cell filopodia.

    • Laleh Abbassi
    • , Stephany El-Hayek
    •  & Hugh J. Clarke

  • Article
    | Open Access

    Sarcopenia is the age-associated functional decline and atrophy of muscle fibers, and it has been proposed that it might be counteracted by inducing myofiber hypertrophy. Here, the authors show that expression levels of the ubiquitin ligase UBR4 are increased with ageing, and that whilst its genetic ablation rescues muscle atrophy, it is also associated with reduced protein quality and impaired force production in Drosophila and mouse models.

    • Liam C. Hunt
    • , Bronwen Schadeberg
    •  & Fabio Demontis

  • Article
    | Open Access

    Muscle atrophy is associated with ageing, but the underlying molecular mechanisms are not well understood. Here, they authors show that ablation of the E3 ubiquitin ligase Mib1 is important for myofibre maintenance via a mechanism that involves targeting and degradation of Actn3, and that Mib1 ablation in mice induces muscle atrophy which can be rescued by knockown of Actn3 expression.

    • Ji-Yun Seo
    • , Jong-Seol Kang
    •  & Young-Yun Kong

  • Review Article
    | Open Access

    Skeletal muscle has a remarkable regenerative capacity, which can largely be attributed to resident muscle stem cells (MuSCs). Here, the authors review the molecular mechanisms regulating MuSC quiescence, activation and proliferation, how these processes are regulated by the stem cell niche, and the role of MuSCs in neuromuscular diseases.

    • F. Relaix
    • , M. Bencze
    •  & Taglietti V.

  • Article
    | Open Access

    Jervell and Lange-Nielsen syndrome is characterised by congenital deafness and vestibular dysfunction, and is caused by mutations in KCNE1 or KCNQ1. Here, the authors show that gene therapy via canalostomy at early postnatal stage can preserve the morphology of inner ear and auditory and vestibular functions in a mouse model of human JLNS2.

    • Xuewen Wu
    • , Li Zhang
    •  & Xi Lin

  • Article
    | Open Access

    The innate immune system and inflammation modulate bone homeostasis through complex regulation of bone remodelling cells including osteoblasts and osteoclasts. Here, the authors show that the type I interferon pathway and guanylate binding proteins functionally limit bone loss by inhibiting osteoclast functions.

    • David E. Place
    • , R. K. Subbarao Malireddi
    •  & Thirumala-Devi Kanneganti

  • Article
    | Open Access

    Endogenous attention is known to be controlled by dorsal fronto-parietal brain areas. Here the authors identify a control attention area located in the temporal lobe, which is functionally distinct from surrounding areas, and is directly connected to parietal and frontal attentional regions.

    • Ilaria Sani
    • , Heiko Stemmann
    •  & Winrich A. Freiwald

  • Review Article
    | Open Access

    Loss of muscle mass is associated with ageing and with a number of diseases such as cancer. Here, the authors review the signaling pathways that modulate protein synthesis and degradation and gain or loss of muscle mass, and discuss therapeutic implications and future directions for the field.

    • Roberta Sartori
    • , Vanina Romanello
    •  & Marco Sandri

  • Article
    | Open Access

    Skeletal muscle conveys the beneficial effects of physical exercise but due to its heterogeneity, studying the effects of exercise on muscle fibres is challenging. Here, the authors carry out proteomic analysis of myofibres from freeze-dried muscle biopsies, show fibre-type specific changes in response to exercise, and show that the oxidative and glycolytic muscle fibers adapt differentially to exercise training.

    • A. S. Deshmukh
    • , D. E. Steenberg
    •  & J. F. P. Wojtaszewski

  • Article
    | Open Access

    Blood and lymphatic vessels bear a strong resemblance but do not share a lumen, thus maintaining their distinct functions. Here, the authors describe that Folliculin, a tumor suppressor, prevents the fusion of these vessels during development by limiting the plasticity of venous and lymphatic endothelial cells.

    • Ikue Tai-Nagara
    • , Yukiko Hasumi
    •  & Yoshiaki Kubota

  • Article
    | Open Access

    Muscle fibers are the largest cells in the body and contain less DNA per unit volume than other cells even if they have multiple nuclei. Here, the authors show that the number of nuclei regulates the cell size with similar scaling properties in mice and humans.

    • Kenth-Arne Hansson
    • , Einar Eftestøl
    •  & Kristian Gundersen

  • Article
    | Open Access

    Skeletal muscle is composed of syncytial myofibres, each containing hundreds of nuclei. Through genetic reduction of the number of nuclei per myofibre, the authors confirm that more nuclei produce larger cells but myofibres with fewer nuclei adaptively compensate leading to larger and functional myonuclear domains.

    • Alyssa A. W. Cramer
    • , Vikram Prasad
    •  & Douglas P. Millay

  • Article
    | Open Access

    To be successful, selective neuromodulation requires a non-invasive method of imaging the fascicular anatomy of peripheral nerves. Here, the authors show the applicability and reliability of fast neural electrical impedance tomography for this purpose and provide its validation against the gold standards of invasive imaging.

    • Enrico Ravagli
    • , Svetlana Mastitskaya
    •  & David Holder

  • Article
    | Open Access

    Duchenne muscular dystrophy (DMD) is characterised by progressive muscle degeneration. Here, the authors show that the BET protein BRD4 is increased in the muscle of DMD mouse models, and that pharmacological inhibition of BRD4 leads to reduced muscle pathology in mice, by modulating NADPH oxidase expression.​

    • Marco Segatto
    • , Roberta Szokoll
    •  & Giuseppina Caretti

  • Article
    | Open Access

    Neurofibromatosis type I (NF1) is characterized by prominent skeletal abnormalities mediated in part by aberrant ERK pathway activation due to NF1 loss-of-function. Here, the authors report the MEKK2 is a key mediator of this aberrant ERK activation and that MEKK2 inhibitors, including ponatinib, ameliorate skeletal defects in a mouse model of NF1.

    • Seoyeon Bok
    • , Dong Yeon Shin
    •  & Matthew B. Greenblatt

  • Article
    | Open Access

    Organ segmentation of whole-body mouse images is essential for quantitative analysis, but is tedious and error-prone. Here the authors develop a deep learning pipeline to segment major organs and the skeleton in volumetric whole-body scans in less than a second, and present probability maps and uncertainty estimates.

    • Oliver Schoppe
    • , Chenchen Pan
    •  & Bjoern H. Menze

  • Article
    | Open Access

    DsbA-L upregulation prevents lipid-induced renal injury in diabetic nephropathy. Here, the authors show that DsbA-L knockout attenuates tubulointerstitial fibrosis in mice, and show that this occurs via activation of Smad3 and p53, which result in modulation of CTGF, a regulator of kidney fibrosis.

    • Xiaozhou Li
    • , Jian Pan
    •  & Dongshan Zhang

  • Article
    | Open Access

    mTORC1 expression is increased during ageing of muscle, and on the other hand, its activation promotes muscle hypertrophy. Here, the authors assess whether mTORC1 has positive or negative effects on ageing, and show that its long-term inhibition preserves muscle mass and function and neuromuscular junction integrity, whereas muscle-specific activation is associated with sarcopenia.

    • Daniel J. Ham
    • , Anastasiya Börsch
    •  & Markus A. Rüegg

  • Article
    | Open Access

    Osteoarthritis (OA) is associated with cartilage disruption, but the underlying mechanisms remain unclear. Here, the authors show that expression of osteoclast-associated receptor (OSCAR) is associated with OA, that its genetic ablation or targeting with OSCAR-Fc fusion protein ameliorates OA in mice by decreasing chondrocyte apoptosis.

    • Doo Ri Park
    • , Jihee Kim
    •  & Soo Young Lee

  • Article
    | Open Access

    High resolution intravascular imaging in the brain is limited by the high tortuosity of the vasculature. Here the authors present a fiber optic imaging technology using high-frequency optical coherence tomography (HF-OCT) to provide volumetric high resolution images in the highly tortuous cerebral vasculature.

    • Giovanni J. Ughi
    • , Miklos G. Marosfoi
    •  & Ajit S. Puri

  • Article
    | Open Access

    Skeletal muscle cells have long been considered to be made primarily of many individual, parallel myofibrils. Here, the authors show that the striated muscle contractile machinery forms a highly branched, mesh-like myofibrillar matrix connected across the entire length and width of the muscle cell.

    • T. Bradley Willingham
    • , Yuho Kim
    •  & Brian Glancy

  • Article
    | Open Access

    Mutations in human PIEZO2, encoding for a mechanosensitive ion channel, lead to skeletal abnormalities including scoliosis and hip dysplasia. Here, the authors show that deletion of Piezo2 in proprioceptive neurons, but not in skeletal lineages, recapitulated the human phenotype in mice.

    • Eran Assaraf
    • , Ronen Blecher
    •  & Elazar Zelzer

  • Article
    | Open Access

    Extravasated erythrocytes in cerebrospinal fluid (CSF) contribute to the pathogenesis of subarachnoid haemorrhage (SAH). Here, the authors show that meningeal lymphatics drain extravasated erythorcytes and that blockage of this drainage aggravates SAH severity.

    • Jinman Chen
    • , Linmei Wang
    •  & Yongjun Wang

  • Article
    | Open Access

    Bone marrow adipose tissue (BMAT) comprises over 10% of total fat mass but its systemic metabolic role is unclear. Here, the authors show that BMAT glucose uptake is not insulin or cold responsive; however, BMAT basal glucose uptake is higher than in white adipose tissue or skeletal muscle, underscoring BMAT’s potential to influence systemic glucose homeostasis.

    • Karla J. Suchacki
    • , Adriana A. S. Tavares
    •  & William P. Cawthorn

  • Article
    | Open Access

    Nebulin-based nemaline myopathy is a heterogenous disease with unclear pathological mechanisms. Here, the authors generate a mouse model that mimics the most common genetic cause of the disease and demonstrate that muscle weakness in this model is associated with twisted actin filaments and altered tropomyosin and troponin behaviour.

    • Johan Lindqvist
    • , Weikang Ma
    •  & Henk Granzier

  • Article
    | Open Access

    Deriving functional pancreatic cell types from human stem cells may have important clinical applications. Building on previous work, here the authors generate stem cell-derived alpha cells via a polyhormonal intermediate, which have a gene expression pattern similar to human islet alpha cells and behave as such when transplanted into mice.

    • Quinn P. Peterson
    • , Adrian Veres
    •  & Douglas A. Melton

  • Article
    | Open Access

    The origin of the heterogeneity of metabolic and inflammatory profiles exhibited by white adipocytes is little understood. Here, using scRNA-seq and computational methods, the authors show that differentiating preadipocytes exhibit gene expression differences and suggest underlying regulators.

    • Alfred K. Ramirez
    • , Simon N. Dankel
    •  & Simon Kasif

  • Article
    | Open Access

    Glucose metabolism is regulated by hypothalamic brain functions and factors produced by peripheral tissues. Here, the authors show that the regulator of food intake Brain-derived neurotrophic factor is also produced and secreted by muscle and stimulates pancreas insulin release.

    • Gianluca Fulgenzi
    • , Zhenyi Hong
    •  & Lino Tessarollo

  • Article
    | Open Access

    Uncoupling protein-1 (UCP1) plays a central role in energy dissipation in brown adipose tissue. Here the authors show that FGF6 and FGF9 induce UCP1 expression in adipocytes and preadipocytes, via modulation of a transcriptional network that is dissociated from brown adipogenesis.

    • Farnaz Shamsi
    • , Ruidan Xue
    •  & Yu-Hua Tseng

  • Article
    | Open Access

    Denervation of muscle fibres induces muscle atrophy, via mechanisms that remain unclear. Here, the authors show that binding of acetylcoline to its receptor at the neuromuscular junction represses the expression of connexins 43 and 45, which promote atrophy, and is sufficient to prevent denervation-induced loss of myofibre mass.

    • Bruno A. Cisterna
    • , Aníbal A. Vargas
    •  & Juan C. Sáez

  • Article
    | Open Access

    An endothelial cell subtype, expressing endomucin and CD31, has been reported to couple angiogenesis with osteogenesis. Here, the authors show that loss of ZEB1 in these cells epigenetically suppresses Notch signaling, leading to impaired angiogenesis and osteogenesis, and that Zeb1 delivery via liposomes ameliorates bone loss in osteoporotic mice

    • Rong Fu
    • , Wen-Cong Lv
    •  & Zhao-Qiu Wu

  • Article
    | Open Access

    Multinucleated giant cells (MGCs) are important in the pathogenesis of various diseases. Here, the authors demonstrate that extracellular presence of the amino acid arginine is required for MGC formation and metabolism, suggesting a translational impact for strategies utilizing systemic arginine depletion in MGC-mediated diseases.

    • Julia S. Brunner
    • , Loan Vulliard
    •  & Gernot Schabbauer

  • Article
    | Open Access

    Sarcopenia is the loss of muscle mass and strength associated with physical disability during ageing. Here, the authors analyse muscle biopsies from 119 patients with sarcopenia and age-matched controls of different ethnic groups and find transcriptional signatures indicating mitochondrial dysfunction, associated with reduced mitochondria numbers and lower NAD+ levels in older individuals with sarcopenia.

    • Eugenia Migliavacca
    • , Stacey K. H. Tay
    •  & Jerome N. Feige

  • Article
    | Open Access

    Skeletal muscle stem cells express the transcription factor Pax7. Here, the authors isolate, from human muscle, cells that are positive for the endothelial marker CLEC14A and show that despite not expressing pax7, these cells regenerate muscle and contribute to the muscle stem cell niche when transplanted into mice.

    • Andreas Marg
    • , Helena Escobar
    •  & Simone Spuler

  • Article
    | Open Access

    The visual word form area (VWFA) is a brain region associated with written language, but it has also been linked to visuospatial attention. Here, the authors reveal distinct structural and functional circuits linking VWFA with language and attention networks, and demonstrate that these circuits separately predict language and attention abilities.

    • Lang Chen
    • , Demian Wassermann
    •  & Vinod Menon

  • Article
    | Open Access

    During high-intensity exercise, muscles convert glucose to lactate, in a process that is energetically less efficient than respiration. Here the authors develop a computational model based on muscle proteomic data showing that bypassing mitochondrial complex I increases ATP production rates, and validate these model predictions in an exercise test on 5 subjects.

    • Avlant Nilsson
    • , Elias Björnson
    •  & Jens Nielsen

  • Article
    | Open Access

    Reactive oxygen species (ROS) stimulate GLUT4-mediated glucose transport following contraction of isolated muscle, but it is not clear if this occurs in vivo. Here, the authors show in human volunteers that exercise induces ROS increase in muscle and, using loss of-function animal models, they demonstrate that NOX2 is a major ROS source required to stimulate glucose uptake during exercise.

    • Carlos Henríquez-Olguin
    • , Jonas R. Knudsen
    •  & Thomas E. Jensen

  • Article
    | Open Access

    Leflunomide is used for the treatment of rheumatoid arthritis. Here, the authors show that effectiveness is limited in patients with higher levels of serum c-reactive protein (CRP). Using animal models, they show that higher CRP induces HIF1a expression, which in turn interferes with Leflunomide signalling, and that effectiveness of the drug is restored when HIF1a is pharmacologically inhibited.

    • Chao Liang
    • , Jie Li
    •  & Aiping Lu

  • Article
    | Open Access

    MR-focused ultrasound can be used to transiently open the blood-brain barrier (BBB). Here, the authors report the results of a first-in-human trial on four patients with amyotrophic lateral sclerosis (ALS), showing that the procedure reversibly permeabilised the BBB in the motor cortex without complications, and suggest that the procedure could in the future be used to increase drug delivery in ALS patients.

    • Agessandro Abrahao
    • , Ying Meng
    •  & Lorne Zinman

  • Article
    | Open Access

    Enamel is the hardest tissue in the body and has been widely studied, yet aspects of its structure remain unclear. Here, the authors report on a study of the orientation and alignment of enamel crystals and challenge previous assumptions.

    • Elia Beniash
    • , Cayla A. Stifler
    •  & Pupa U. P. A. Gilbert

  • Article
    | Open Access

    HuR is an RNA-binding protein that regulates myotube differentiation in vitro. Here, the authors show that the muscle-specific ablation of HuR in mice leads to enhanced endurance capacity and an increase in oxidative fibres by destabilising PGC1α-mRNA, and show that the mice are protected against cancer cachexia

    • Brenda Janice Sánchez
    • , Anne-Marie K. Tremblay
    •  & Imed-Eddine Gallouzi

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