Anatomy

  • Article
    | Open Access

    The cellular identity and function of the pancreatic polypeptide (Ppy)-producing γ-cells are incompletely understood. Here the authors show that these cells are heterogeneous and display adaptive plasticity to engage in insulin production following β-cell injury, but loss of the Ppy gene or γ-cells in mice does not affect weight or glycemia under basal conditions.

    • Marta Perez-Frances
    • , Léon van Gurp
    •  & Pedro L. Herrera
  • Article
    | Open Access

    While many genetic loci have been found to be associated with disease, not many have had their causal variants and mechanisms investigated. Here, the authors experimentally dissect two loci near GDF5 which are associated with two different joint disorders and which map to independent regulatory elements.

    • Pushpanathan Muthuirulan
    • , Dewei Zhao
    •  & Terence D. Capellini
  • Article
    | Open Access

    The gene regulatory network controlling the bifurcation of common progenitors into the neural retina and retinal-pigmented epithelium programs remains poorly understood. Here the authors study transcriptome dynamics and chromatin accessibility during this process in zebrafish, revealing network redundancy, as well as context-dependent and sequential transcription factor activity.

    • Lorena Buono
    • , Jorge Corbacho
    •  & Juan-Ramón Martínez-Morales
  • Article
    | Open Access

    Many animals, including mammals and insects, like slightly acidic yet dislike highly acidic foods, but how animals discriminate low from high acidity is unclear. Here the authors demonstrate that the fruit fly uses an evolutionarily conserved taste receptor to distinguish low from high concentrations of acid.

    • Tingwei Mi
    • , John O. Mack
    •  & Yali V. Zhang
  • Article
    | Open Access

    Regular exercise promotes overall health and prevents non-communicable diseases, but the adaptation mechanisms are unclear. Here, the authors perform a meta-analysis to reveal time-specific patterns of the acute and long-term exercise response in human skeletal muscle, and identify sex- and age-specific changes.

    • David Amar
    • , Malene E. Lindholm
    •  & Euan A. Ashley
  • Article
    | Open Access

    Antibody-based Wnt agonists are able to phenocopy Wnt signaling in vivo resulting in increased bone density, repair, and strength. Here, the authors show that Wnt agonists can reverse bone loss associated with ovariectomy and build stronger bone when administered after fracture.

    • Tristan W. Fowler
    • , Troy L. Mitchell
    •  & Yang Li
  • Article
    | Open Access

    Small-angle X-ray scattering (SAXS) combines the high tissue penetration of X-rays with specificity to periodic nanostructures. The authors use SAXS tensor tomography (SAXS-TT) on intact mouse and human brain tissue samples, to quantify myelin levels and determine myelin integrity, myelinated axon orientation, and fibre tracts non-destructively.

    • Marios Georgiadis
    • , Aileen Schroeter
    •  & Markus Rudin
  • Article
    | Open Access

    Differences in thalamic structure have been observed in several psychiatric disorders, but the genetic overlap has not been explored. Here, the authors perform a genome-wide association study on thalamic nuclei volume and find genetic loci in common between thalamic volumes and brain disorders.

    • Torbjørn Elvsåshagen
    • , Alexey Shadrin
    •  & Tobias Kaufmann
  • Article
    | Open Access

    Supplementation of magnesium (Mg2+) or its inclusion in biomaterials has beneficial effects for bone formation, but it has also been reported that it can have detrimental effects. Here, the authors analyse dose- and time-dependent effects of Mg2+ on bone regeneration and show that it can stimulate monocyte-macrophage lineage cells to support bone formation in the early phases of repair, but inhibit bone repair and mineralization in later stages by promoting a pro-inflammatory environment.

    • Wei Qiao
    • , Karen H. M. Wong
    •  & Kelvin W. K. Yeung
  • Article
    | Open Access

    Osteocytes are the master regulatory cells within the skeleton. Here, the authors map the transcriptome of osteocytes from diverse skeletal sites, ages and between sexes and identify an osteocyte transcriptome signature associated with rare skeletal disorders and common complex skeletal diseases.

    • Scott E. Youlten
    • , John P. Kemp
    •  & Peter I. Croucher
  • Article
    | Open Access

    The mechanism by which parathyroid hormone mediates the switch from bone resorption to bone formation is unclear. Here, the authors show that SLPI regulates the communication between osteoblasts and osteoclasts to promote the anabolic effect of parathyroid hormone.

    • Akito Morimoto
    • , Junichi Kikuta
    •  & Masaru Ishii
  • Article
    | Open Access

    As human skeletal muscle ages, gene expression programs change and reflect damage accumulation and homeostatic resilience mechanisms. Here, the authors present a detailed framework of the global transcriptome that characterizes skeletal muscle during aging in healthy individuals.

    • Robert A. Tumasian III
    • , Abhinav Harish
    •  & Luigi Ferrucci
  • Article
    | Open Access

    The functional relationship between subchondral bone and articular cartilage is unclear. Here, the authors show that transforming growth factor-beta propagates the mechanical impact of subchondral bone on articular cartilage through αV integrin–talin mechanical transduction system in chondrocytes.

    • Gehua Zhen
    • , Qiaoyue Guo
    •  & Xu Cao
  • 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