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| Open AccessSmall molecule screen in embryonic zebrafish using modular variations to target segmentation
Chemical screens can identify small molecules that affect biological development, with potential therapeutic value. Here, the authors use a modular approach in a screen in zebrafish embryos, varying concentration, genotype and timing to target segmentation disorders, birth defects that affect the spinal column.
- Sandra Richter
- , Ulrike Schulze
- & Andrew C. Oates
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Article
| Open AccessGeneration of interspecies limited chimeric nephrons using a conditional nephron progenitor cell replacement system
The transplantation of tissue-specific progenitor cells may be an approach in organ regeneration. Here the authors show that the nephron progenitor population of a developing mouse kidney, when ablated, can be replaced by exogenously supplied rat nephron progenitors, generating interspecies nephrons.
- S. Yamanaka
- , S. Tajiri
- & T. Yokoo
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| Open AccessConstruction of developmental lineage relationships in the mouse mammary gland by single-cell RNA profiling
The mammary epithelium comprises two cell lineages but the heterogeneity amongst these during development is unclear. Here, the authors report single-cell RNA sequencing of the mouse mammary epithelium at four developmental stages, revealing diversity in both compartments and a transcriptional shift with puberty onset.
- Bhupinder Pal
- , Yunshun Chen
- & Jane E. Visvader
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| Open AccessTransient cardiomyocyte fusion regulates cardiac development in zebrafish
Cell fusion regulates several physiological events, for example, fusion of myoblasts in skeletal muscle formation, but it is unclear if this process occurs in the heart. Here, the authors use transgenic reporters in zebrafish to show transient cardiomyocyte fusion, modulating cardiac development and function.
- Suphansa Sawamiphak
- , Zacharias Kontarakis
- & Didier Y. R. Stainier
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| Open AccessOdd skipped-related 1 identifies a population of embryonic fibro-adipogenic progenitors regulating myogenesis during limb development
Fibro-adipogenic progenitors (FAPs) form part of interstitial muscle connective tissue (MCT) in adults but the origin of this non-myogenic lineage is unclear. Here, the authors show that Odd skipped related 1 (Osr1) in mice marks embryonic MCT, giving rise to FAPs, and loss of Osr1 in the limb causes muscle defects.
- Pedro Vallecillo-García
- , Mickael Orgeur
- & Sigmar Stricker
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| Open AccessStochastic priming and spatial cues orchestrate heterogeneous clonal contribution to mouse pancreas organogenesis
The pancreas arises from a small population of cells but how individual cells contribute to organ formation is unclear. Here, the authors deconstruct pancreas organogenesis into clonal units, showing that single progenitors give rise to heterogeneous multi-lineage and endocrinogenic single-lineage clones.
- Hjalte List Larsen
- , Laura Martín-Coll
- & Anne Grapin-Botton
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| Open AccessCo-option of the cardiac transcription factor Nkx2.5 during development of the emu wing
The transcription factor Nkx2.5 is essential for heart development. Here, the authors identify a previously unknown expression domain for Nkx2.5 in the emu wing and explore its role in diminished wing bud development in the flightless emu, compared with three other birds that have functional wings.
- Peter G. Farlie
- , Nadia M. Davidson
- & Craig A. Smith
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| Open AccessThe microprotein Minion controls cell fusion and muscle formation
Cellular fusion is essential for skeletal muscle development. Here the authors identify Minion as a microprotein required for myoblast fusion and skeletal muscle formation, and show that co-expression of Minion and Myomaker is sufficient to induce cytoskeletal rearrangement and cell fusion even in non-muscle cells.
- Qiao Zhang
- , Ajay A. Vashisht
- & Srihari C. Sampath
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Article
| Open AccessMyomerger induces fusion of non-fusogenic cells and is required for skeletal muscle development
Cellular fusion is fundamental for skeletal muscle development. Here the authors show that myomerger is expressed in myoblasts, is essential for myoblast fusion in mice, and in co-operation with myomaker confers fusogenic ability to non-fusogenic cells.
- Malgorzata E. Quinn
- , Qingnian Goh
- & Douglas P. Millay
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| Open AccessSfrp5 identifies murine cardiac progenitors for all myocardial structures except for the right ventricle
It is unclear which progenitors define different regions of the heart. Here, the authors find Secreted frizzled-related protein 5 is expressed in murine progenitor cells for the outflow tract, first heart field, and sinus venosus, but not the right ventricle, and Wnt inhibition prevents progenitor proliferation.
- Masayuki Fujii
- , Akane Sakaguchi
- & Hiroki Kokubo
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| Open AccessPervasive translational regulation of the cell signalling circuitry underlies mammalian development
Gene expression is regulated at several levels, including through the modulation of protein translation. Here the authors find that translation control diversifies gene expression between developing tissues and regulates major signalling pathways through a complex landscape of upstream open reading frames (uORFs).
- Kotaro Fujii
- , Zhen Shi
- & Maria Barna
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Article
| Open AccessFoxa2 identifies a cardiac progenitor population with ventricular differentiation potential
The progenitor populations that contribute to the key cardiac lineages in a chamber-specific manner are unknown. Here, the authors identifyFoxa2+ progenitor population, which is specified at gastrulation, as contributing primarily to cardiovascular cells of both ventricles and the epicardium in mice.
- Evan Bardot
- , Damelys Calderon
- & Nicole C. Dubois
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| Open AccessStepwise reprogramming of liver cells to a pancreas progenitor state by the transcriptional regulator Tgif2
Liver and pancreas cells arise from a common endoderm progenitor in the embryo, but what regulates their cell fate is unclear. Here, the authors show that expression of the Three-Amino-acid-Loop-Extension (TALE) homeobox TG-interacting factor 2 (TGIF2) in hepatocytes reprogrammes the cells to a pancreatic fate.
- Nuria Cerdá-Esteban
- , Heike Naumann
- & Francesca M. Spagnoli
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Article
| Open AccessJAK/STAT controls organ size and fate specification by regulating morphogen production and signalling
Morphogens regulate growth and pattern in vertebrate and invertebrate limbs. Here, the authors show that the JAK/STAT pathway promotes the growth of the Hedgehog-producing cell population in theDrosophilawing, thereby allowing the stable localization of the BMP/Dpp organizer.
- Carles Recasens-Alvarez
- , Ana Ferreira
- & Marco Milán
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| Open AccessHedgehog–BMP signalling establishes dorsoventral patterning in lateral plate mesoderm to trigger gonadogenesis in chicken embryos
Ingression of cells from the lateral plate mesoderm (LPM) initiates gonad differentiation but how these events are triggered is unclear. Here, the authors show that gonadal progenitor cells at the ventromedial LPM initiate gonadogenesis, and are activated by Hedgehog and BMP4 signalling.
- Takashi Yoshino
- , Hidetaka Murai
- & Daisuke Saito
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Article
| Open AccessEndothelial cells are progenitors of cardiac pericytes and vascular smooth muscle cells
Pericytes and vascular smooth muscle cells are crucial for functional blood vessels, but the developmental sources of these cells are incompletely understood. Here, the authors show that endocardial endothelial cells give rise to cardiac mural cells, which are controlled by Wnt signalling.
- Qi Chen
- , Hui Zhang
- & Ralf H. Adams
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Article
| Open Accessβ-Catenin C-terminal signals suppress p53 and are essential for artery formation
How p53 is restrained in arterial maturation during embryonic development is unclear. Here, the authors show that β-catenin C-terminal interactions inhibit CREB binding protein-mediated acetylation and activation of p53 in smooth muscle cells, and that this function is essential for artery formation.
- Dario F. Riascos-Bernal
- , Prameladevi Chinnasamy
- & Nicholas E. S. Sibinga
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Article
| Open AccessNuclear receptor NR5A2 controls neural stem cell fate decisions during development
The molecular signals regulating the decision of neural stem cells (NSC) to proliferate versus differentiate are unclear. Here, the authors identify the nuclear receptor NR5A2 as coordinating cell-cycle exit with differentiation of NSCs via direct actions on Ink4, Prox1, Notch1 and JAK/STAT.
- Athanasios Stergiopoulos
- & Panagiotis K. Politis
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| Open Access14-3-3 proteins regulate Tctp–Rheb interaction for organ growth in Drosophila
14-3-3 proteins regulate several signalling pathways but often act redundantly; however, the molecular mechanisms behind such redundancy are unclear. Here, the authors show that 14-3-3 proteins regulate two interacting components of Tor signalling in Drosophila, Tctp and Rheb, disrupting organ development.
- Thao Phuong Le
- , Linh Thuong Vuong
- & Kwang-Wook Choi
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| Open AccessLaminin regulates PDGFRβ+ cell stemness and muscle development
Muscle PDGFRβ+ cells are interstitial stem/progenitor cells with myogenic potential. Here, Yao et al. show that PDGFRβ+cell-derived laminin actively regulates their proliferation, differentiation and fate determination.
- Yao Yao
- , Erin H. Norris
- & Sidney Strickland
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| Open AccessEssential role for a novel population of binucleated mammary epithelial cells in lactation
The main function of the mammary gland is to produce milk to sustain offspring. Here, the authors show that secretory alveolar cells in the lactating gland in several species are binucleated, which increases milk production, and that binucleation is regulated by Aurora kinase-A and Polo-like kinase-1.
- Anne C. Rios
- , Nai Yang Fu
- & Jane E. Visvader
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| Open AccessRepulsive cues combined with physical barriers and cell–cell adhesion determine progenitor cell positioning during organogenesis
The precise positioning of organ progenitor cells is essential for organ development and function. Here the authors use live imaging and mathematical modelling to show that the confinement of a motile progenitor cell population results from coupled physical barriers and cell-cell interactions.
- Azadeh Paksa
- , Jan Bandemer
- & Erez Raz
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| Open AccessThe cell adhesion molecule Fasciclin2 regulates brush border length and organization in Drosophila renal tubules
In Drosophila, Fasciclin 2 (Fas2) has been mainly studied in the nervous system, yet this adhesion protein is more abundant in the adult renal tubule. Here the authors show that Fas2 is essential for brush border maintenance in renal tubules through regulation of microvilli length and organization.
- Kenneth A. Halberg
- , Stephanie M. Rainey
- & Julian A. T. Dow
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| Open AccessStabilin-2 modulates the efficiency of myoblast fusion during myogenic differentiation and muscle regeneration
Phosphatidylserine and its receptors are associated with cell-cell fusion. Here, the authors show the phosphatidylserine receptor stabilin-2 is expressed by muscle cells and plays a vital role in myoblast fusion and post-injury muscle regeneration in mice.
- Seung-Yoon Park
- , Youngeun Yun
- & In-San Kim
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Article
| Open AccessALDH1A1 provides a source of meiosis-inducing retinoic acid in mouse fetal ovaries
Recent findings have challenged the established concept that retinoic acid (RA) induces foetal germ cells to enter meiosis. Here, Bowles et al. identify the enzyme ALDH1A1 as a source of ovarian RA that may induce meiosis even when other RA-synthetic enzymes are deleted.
- Josephine Bowles
- , Chun-Wei Feng
- & Peter Koopman
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| Open AccessAutophagy regulates Notch degradation and modulates stem cell development and neurogenesis
The molecular mechanisms behind how autophagy may impact on developmental pathways and cell fate decisions are unclear. Here Wu et al.identify Notch receptors being taken up into ATG16L1-positive autophagosomes and, using a mouse mutant model, show that changes in autophagy can impact on stem cell fate.
- Xiaoting Wu
- , Angeleen Fleming
- & David C. Rubinsztein
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| Open AccessE2F function in muscle growth is necessary and sufficient for viability in Drosophila
The transcriptional regulators E2F/Dp play a critical role in cell-cycle regulation, but it is unclear why E2F-deficient flies die. Here, the authors show this is linked to the function of E2F in adult Drosophilaskeletal muscle, with the contribution of E2f1 being most important in post-fusion muscle.
- Maria Paula Zappia
- & Maxim V. Frolov
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Article
| Open AccessCLIC4 regulates apical exocytosis and renal tube luminogenesis through retromer- and actin-mediated endocytic trafficking
Chloride intracellular channel (CLIC) 4 is an ion channel, localized in the cytoplasm, and first identified as an actin binding protein. Here, Chou et al.knockout CLIC4 in mice and observe tubulogenesis and renal proximal tubule dilation defects, which is caused by irregular actin and endosomal trafficking.
- Szu-Yi Chou
- , Kuo-Shun Hsu
- & Ching-Hwa Sung
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Linc-YY1 promotes myogenic differentiation and muscle regeneration through an interaction with the transcription factor YY1
Long intervening noncoding RNAs (lincRNAs) are an emerging class of molecular regulators with diverse functions. Here the authors identify Linc-YY1, a novel lincRNA transcribed from the noncoding region of the mouse YY1 gene, that binds to YY1 protein and thereby regulates skeletal muscle differentiation and regeneration.
- Liang Zhou
- , Kun Sun
- & Huating Wang
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Article
| Open AccessCX3CR1 deficiency promotes muscle repair and regeneration by enhancing macrophage ApoE production
Chemokine-driven infiltration of inflammatory macrophages is central to the muscle regenerative response to injury. Here the authors show that the function of infiltrating macrophages is also important as notexin-induced muscle injury in mice is rescued by CX3CR1 knockout owing to enhanced ApoE production.
- Ludovic Arnold
- , Hélène Perrin
- & Christophe Combadiere
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| Open AccessAn orphan gene is necessary for preaxial digit formation during salamander limb development
The first digits to form in salamanders are the two most anterior ones, unlike in other tetrapods. Here, the authors show that the gene Prod1is expressed during early outgrowth of the limb bud and is necessary for limb formation in salamanders.
- Anoop Kumar
- , Phillip B. Gates
- & Jeremy P. Brockes
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| Open AccessAn intrinsic timer specifies distal structures of the vertebrate limb
The specification of positional values along the proximo-distal axis (shoulder to digits) of the vertebrate limb is an unresolved issue. By using heterochronic transplants of distal mesenchyme, the authors show that the zeugopod and autopod (elbow to digits) are progressively specified in an intrinsically timed manner.
- Patricia Saiz-Lopez
- , Kavitha Chinnaiya
- & Matthew Towers
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| Open AccessTurning terminally differentiated skeletal muscle cells into regenerative progenitors
Newts can regenerate amputated limbs via unknown mechanism involving dedifferentiation of cells in the stump into progenitors that contribute to the new appendages. Here the authors show that skeletal muscle dedifferentiation in regenerating newt limbs relies on a diverted programmed cell death response by myofibers.
- Heng Wang
- , Sara Lööf
- & András Simon
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MicroRNA-431 accelerates muscle regeneration and ameliorates muscular dystrophy by targeting Pax7 in mice
Skeletal muscle stem cells (satellite cells) express different levels of a critical transcriptional regulator Pax7. Here, the authors show that miR-431 regulates Pax7 levels in satellite cells of the developing and regenerating muscle, and that increased miR-431expression in these cells alleviates symptoms of muscular dystrophy in mice.
- Rimao Wu
- , Hu Li
- & Dahai Zhu
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Mitotic cell rounding and epithelial thinning regulate lumen growth and shape
The regulation of lumen formation and dimension is a key question in organ morphogenesis. Using the zebrafish inner ear as a model, here the authors show that the growth of a cavity depends on epithelial thinning and mitotic cell rounding.
- Esteban Hoijman
- , Davide Rubbini
- & Berta Alsina
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Analysis of opo cis-regulatory landscape uncovers Vsx2 requirement in early eye morphogenesis
The transcriptional regulation of morphogenetic effectors during eye development is poorly understood. Here, the authors show that transcription of an endocytosis regulator Opois crucial for the neural retina development in zebrafish and activated by the interaction of the transcription factor Vsx2 and retinal enhancer H6_10137.
- Ines Gago-Rodrigues
- , Ana Fernández-Miñán
- & Juan R. Martinez-Morales
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Yes-associated protein regulates endothelial cell contact-mediated expression of angiopoietin-2
Angiogenesis is regulated by dynamic changes in endothelial cell contact. Here, the authors show that signals from endothelial cell junctions affect the subcellular localization and function of Yes-associated protein, ultimately modifying angiopoietin-2 expression and angiogenic activity of endothelial cells.
- Hyun-Jung Choi
- , Haiying Zhang
- & Young-Guen Kwon
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Lineage specification of ovarian theca cells requires multicellular interactions via oocyte and granulosa cells
Lineage establishment of theca cells is essential for follicle development and morphogenesis of the ovary. Here the authors provide genetic evidence for the origins of theca progenitor cells and study the mechanisms critical for their differentiation.
- Chang Liu
- , Jia Peng
- & Humphrey H.-C. Yao
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Histone deacetylation promotes mouse neural induction by restricting Nodal-dependent mesendoderm fate
Differentiation of embryonic stem cells (ESCs) into neural lineages involves epigenetic changes. Here the authors show that transient histone deacetylation promotes the transition from epiblast stem cells to neural progenitors during mouse ESC differentiation and show that this effect is partly mediated by the restriction of Nodal signalling by histone deacetylase 1.
- Pingyu Liu
- , Xiaoyang Dou
- & Naihe Jing
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Article
| Open AccessMolecular development of chondrichthyan claspers and the evolution of copulatory organs
Claspers are copulatory organs found in male cartilaginous fishes. Here, the authors show that androgen receptor signalling maintains the Shh pathway to promote clasper development in male skates and suggest the importance of hormonal regulation in the evolution of male copulatory organs.
- Katherine L. O’Shaughnessy
- , Randall D. Dahn
- & Martin J. Cohn
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Article
| Open AccessEphB4 forward signalling regulates lymphatic valve development
The bidirectional Eph-ephrin signalling regulates a myriad of developmental programmes. Zhang et al. show that EphB4 forward signalling is crucial for lymphatic valve development, providing new insight into this important developmental process previously thought to be regulated by ephrinB2-dependent reverse signalling.
- Gu Zhang
- , John Brady
- & Minhong Yan
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The transcription factor Foxc1 is necessary for Ihh–Gli2-regulated endochondral ossification
Skeletal development relies on endochondral ossification. Here the authors show that transcription factors Foxc1 and Gli2 interact to modulate expression of Ihh target genes that control endochondral ossification, and that disruption of this interaction partly underlies skeletal disorders in the Axenfeld–Rieger syndrome.
- Michiko Yoshida
- , Kenji Hata
- & Toshiyuki Yoneda
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The Hippo pathway effector YAP is a critical regulator of skeletal muscle fibre size
The Yes-associated protein (YAP) is a core effector of the Hippo pathway, which regulates proliferation and apoptosis in organ development, but its function in adult skeletal muscle remains poorly defined. Here the authors show that YAP is an essential regulator of myofibre size in adult skeletal muscle, via interaction with TEAD transcription factors.
- K. I. Watt
- , B. J. Turner
- & P. Gregorevic
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The ubiquitin ligase PDZRN3 is required for vascular morphogenesis through Wnt/planar cell polarity signalling
Wnt/planar cell polarity (PCP) signalling regulates angiogenesis in vertebrates. Here the authors show that the E3 ubiquitin ligase PDZRN3 ubiquitinates the PCP-signalling protein Dishevelled 3 to promote Wnt/PCP signalling, directing embryonic and postnatal remodelling of the vasculature in mouse.
- Raj N. Sewduth
- , Béatrice Jaspard-Vinassa
- & Cécile Duplàa
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WT1 controls antagonistic FGF and BMP-pSMAD pathways in early renal progenitors
The transcription factor Wilms’ tumour 1 (WT1) regulates kidney development, and Wt1 mutations are associated with renal cancer. Here the authors identify WT1 target genes in renal progenitors during early kidney development in mouse embryos and show that loss of Wt1suppresses FGF and induces BMP signalling.
- Fariba Jian Motamedi
- , Danielle A. Badro
- & Andreas Schedl
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Article
| Open AccessSonic hedgehog-expressing cells in the developing limb measure time by an intrinsic cell cycle clock
During vertebrate limb patterning the morphogen Sonic Hedgehog (Shh) is produced by cells of the polarizing region (ZPA). Here, the authors show, using chick embryo grafting experiments, that the duration of Shh expression by ZPA cells is defined by a cell cycle clock that is started and can also be reset by changes in retinoic acid signalling.
- Kavitha Chinnaiya
- , Cheryll Tickle
- & Matthew Towers
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| Open AccessmicroRNA input into a neural ultradian oscillator controls emergence and timing of alternative cell states
Hes1 is an important regulator of progenitor maintenance and timed differentiation, which shows oscillatory expression. Here, the authors combine experimental data and mathematical modelling to show that the interaction between miRNA-9 and Hes1 can predict progenitor transition from one cell state to another, as well as the timing of this transition.
- Marc Goodfellow
- , Nicholas E. Phillips
- & Nancy Papalopulu
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Arid5b facilitates chondrogenesis by recruiting the histone demethylase Phf2 to Sox9-regulated genes
The transcription factor Sox9 together with its co-regulators promotes chondrocyte differentiation. Here Hata et al.find that Arid5b acts as a transcriptional co-regulator of Sox9 by regulating histone demethylation of Sox9 target genes during chondrogenesis in mice.
- Kenji Hata
- , Rikako Takashima
- & Toshiyuki Yoneda
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MG53-induced IRS-1 ubiquitination negatively regulates skeletal myogenesis and insulin signalling
The protein MG53 is known to inhibit myogenesis. Here, Ko et al. show that MG53 is an E3 ubiquitin ligase that mediates degradation of insulin receptor substrate 1 in skeletal muscle, thereby regulating myogenesis and insulin sensitivity in vitro and in vivo.
- Jae-Sung Yi
- , Jun Sub Park
- & Young-Gyu Ko