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| Open AccessDephosphorylated parafibromin is a transcriptional coactivator of the Wnt/Hedgehog/Notch pathways
Normal epithelial intestine organisation requires Wnt and Hedgehog signalling activity. Here, the authors show that parafibromin can activate both pathways in a mutually exclusive manner and is important for intestinal homeostasis.
- Ippei Kikuchi
- , Atsushi Takahashi-Kanemitsu
- & Masanori Hatakeyama
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Article
| Open AccessTargeting of Fzr/Cdh1 for timely activation of the APC/C at the centrosome during mitotic exit
The activity of the anaphase-promoting complex/cyclosome (APC/C) needs to be regulated in time and space to perform different functions. Here the authors show that Spd2 localizes the APC/C activator Fzr at the centrosomes to promote optimal APC/C activity towards its centrosomal substrate Aurora A.
- Francesco Meghini
- , Torcato Martins
- & Yuu Kimata
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Article
| Open AccessLATS-YAP/TAZ controls lineage specification by regulating TGFβ signaling and Hnf4α expression during liver development
The Hippo pathway regulates the differentiation of stem and progenitor cells, but it is unclear how it acts in liver development. Here, the authors knockout Hippo pathway components Lats1 and 2in the liver, causing suppression of hepatocyte differentiation but promoting biliary cell differentiation.
- Da-Hye Lee
- , Jae Oh Park
- & Dae-Sik Lim
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Article
| Open AccessMYC/MIZ1-dependent gene repression inversely coordinates the circadian clock with cell cycle and proliferation
The circadian clock and the cell cycle systems coordinate global physiology. Here the authors show that MYC represses the clock genes, together with MIZ1, and induces proliferation, suggesting that MYC inversely modulates cell cycle and circadian clock genes.
- Anton Shostak
- , Bianca Ruppert
- & Michael Brunner
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Article
| Open AccessHomotypic cell competition regulates proliferation and tiling of zebrafish pigment cells during colour pattern formation
Melanophores, iridophores and xanthophores are pigment-cell types that interact to form the stripes in zebrafish. Here, the authors study the interaction between cells of the same kind and show that each pigment-cell type covers the skin by contact based competition.
- Brigitte Walderich
- , Ajeet Pratap Singh
- & Christiane Nüsslein-Volhard
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| Open AccessComparative analysis of ear-hole closure identifies epimorphic regeneration as a discrete trait in mammals
The extent to which mammals and other vertebrates share similar mechanisms of tissue regeneration is unclear. Here, the authors use an ear punch assay in spiny mice, which regenerate fully, to show blastema formation and mesenchymal cell proliferation as cell cycle regulators p21 and p27 remain cytoplasmic.
- Thomas R. Gawriluk
- , Jennifer Simkin
- & Ashley W. Seifert
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| Open AccessEpidermal Notch1 recruits RORγ+ group 3 innate lymphoid cells to orchestrate normal skin repair
In normal skin, Notch directs keratinocytes to terminally differentiate. Here the authors show that Notch1 has a wider role in skin repair; Notch1 is activated in keratinocytes after damage and drives transcription of TNFα and inflammatory chemokines, which in turn recruit ILC3s and macrophages that promote repair.
- Zhi Li
- , Tom Hodgkinson
- & Carrie A. Ambler
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Article
| Open AccessThe TLX-miR-219 cascade regulates neural stem cell proliferation in neurodevelopment and schizophrenia iPSC model
Dysregulation of microRNAs has been implicated in neurodevelopmental disorders, including schizophrenia. Here the authors show that the TLX-miR-219 cascade regulates the proliferation of neural stem cells during normal development, and this pathway is dysregulated in a schizophrenia iPSC model.
- Kiyohito Murai
- , Guoqiang Sun
- & Yanhong Shi
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Article
| Open AccessBTG2 bridges PABPC1 RNA-binding domains and CAF1 deadenylase to control cell proliferation
BTG2 promotes mRNA poly(A) tail shortening and regulates cellular differentiation. Here, Stupfler et al. show that the BTG2 APRO domain interacts with PABPC1 RRM1, allowing the former to recruit and stimulate the poly(A) tail shortening activity of CAF1 deadenylase and to control cell proliferation.
- Benjamin Stupfler
- , Catherine Birck
- & Fabienne Mauxion
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Article
| Open AccessHaematopoietic ESL-1 enables stem cell proliferation in the bone marrow by limiting TGFβ availability
Hematopoietic stem and progenitor cell (HSPCs) proliferation is controlled by signals from the niche. Here, Leivaet al. show in vivoin mice that deletion of E-selectin ligand 1 causes quiescence of HSPCs and a reduction in niche size, which is mediated by changes of TGFß levels in the bone marrow.
- Magdalena Leiva
- , Juan A. Quintana
- & Andrés Hidalgo
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Article
| Open AccessReconciling diverse mammalian pigmentation patterns with a fundamental mathematical model
How embryonic melanoblast behaviour influences adult pigmentation patterns and causes patterning defects is unclear. Here, Mort et al. construct a stochastic model parameterised experimentally to show that melanoblast migration is undirected and that reduced proliferation causes patterning defects.
- Richard L. Mort
- , Robert J. H. Ross
- & Christian A. Yates
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Article
| Open AccessConcurrent BMP7 and FGF9 signalling governs AP-1 function to promote self-renewal of nephron progenitor cells
The growth factors BMP and FGF both stimulate the self-renewal of nephron progenitor cells (NPCs), but how these signals overlap is unclear. Here in the mouse, Muthukrishnan et al. find BMP7 and FGF9 coordinately regulate AP-1 transcriptional activity, promoting G1-S cell cycle progression and NPC proliferation.
- Sree Deepthi Muthukrishnan
- , Xuehui Yang
- & Leif Oxburgh
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| Open AccessESRP2 controls an adult splicing programme in hepatocytes to support postnatal liver maturation
Alternative RNA splicing is important during organismal development. Here, the authors perform RNA-Seq on mouse and human liver samples to provide a comprehensive view of splicing events during liver development and growth, and identify Espr2 as a main regulator of these splicing processes.
- Amruta Bhate
- , Darren J. Parker
- & Auinash Kalsotra
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| Open AccessInhibition of DYRK1A and GSK3B induces human β-cell proliferation
All forms of diabetes eventually lead to a reduction in insulin-secreting pancreatic β-cells. Here, the authors report aminopyrazine derivatives, which induce proliferation of rodent as well as human β-cells and improve glucose metabolism in a mouse model of type 1 diabetes.
- Weijun Shen
- , Brandon Taylor
- & Bryan Laffitte
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Article
| Open AccessPTEN mediates Notch-dependent stalk cell arrest in angiogenesis
During the formation of vascular sprouts, Notch activation inhibits proliferation of the stalk ECs via unknown mechanism. Here the authors show that PTEN represents a critical mediator of Notch anti-proliferative response in stalk cells via its phosphatase-dependent and -independent activity.
- Helena Serra
- , Iñigo Chivite
- & Mariona Graupera
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| Open AccessPrmt5 is a regulator of muscle stem cell expansion in adult mice
Skeletal muscle satellite cells are important for muscle regeneration, but their regulatory mechanisms are largely unknown. Here the authors identify arginine methyltransferase Prmt5 as a key regulator of satellite cell maintenance and function in adult mice, and show that Prmt5 acts mainly but not exclusively on the cell cycle inhibitor p21.
- Ting Zhang
- , Stefan Günther
- & Thomas Braun
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| Open AccessCyclic stretching of soft substrates induces spreading and growth
Cells grown on a stiff substrate are stimulated through physical cues to spread, create actin stress fibres and proliferate. Here Cui et al. show that cyclic stretching cells on a soft pillar substrate has the same effect as growth on a stiff substrate, and results in nuclear translocation of YAP and MRTF-A.
- Yidan Cui
- , Feroz M. Hameed
- & Michael Sheetz
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Article
| Open AccessOncogenic Kit signals on endolysosomes and endoplasmic reticulum are essential for neoplastic mast cell proliferation
Activating mutations of the tyrosine kinase Kit are commonly found in mast cell neoplasms and gastrointestinal stromal tumours. Here the authors show that mutant Kit, through the activation of PI3K and STAT3 pathways, elicits proliferative and survival signals from endolysosomes and from the endoplasmic reticulum.
- Yuuki Obata
- , Shota Toyoshima
- & Ryo Abe
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| Open AccessPHD3 regulates EGFR internalization and signalling in tumours
PHD3 is a hypoxia-inducible prolyl hydroxylase that regulates stability of HIF-1. Here Garvalov et al.report a hydroxylase-independent role of PHD3 in gliomas as a scaffolding protein that promotes internalization and limits signalling of EGFR upon ligand binding, thus inhibiting growth in hypoxia.
- Boyan K. Garvalov
- , Franziska Foss
- & Till Acker
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PINK1 deficiency sustains cell proliferation by reprogramming glucose metabolism through HIF1
Loss of function of the kinase PINK1 is associated with familial early-onset Parkinson’s disease and impaired clearance of damaged mitochondria. Here the authors show that the resulting oxidative stress activates the hypoxia regulator HIF1α, resulting in increased glycolysis and cell proliferation.
- Raquel Requejo-Aguilar
- , Irene Lopez-Fabuel
- & Juan P. Bolaños
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Increased Notch signalling inhibits anoikis and stimulates proliferation of prostate luminal epithelial cells
Prostate epithelia contain basal, luminal and neuroendocrine cells. Here the authors show that overexpression of the Notch intracellular domain in the mouse prostate promotes proliferation and suppresses anoikis of prostate luminal epithelial cells.
- Oh-Joon Kwon
- , Joseph M. Valdez
- & Li Xin
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The splicing activator DAZAP1 integrates splicing control into MEK/Erk-regulated cell proliferation and migration
DAZAP1 is a multi-functional RNA-binding protein that affects diverse aspects of RNA metabolism. Here, Choudhury et al.demonstrate that DAZAP1 acts as a general splice activator regulated by MEK/ERK signalling and thereby serves to integrate splice control into the regulation of cellular proliferation.
- Rajarshi Choudhury
- , Sreerupa Ghose Roy
- & Zefeng Wang
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Thymic epithelial cell expansion through matricellular protein CYR61 boosts progenitor homing and T-cell output
Thymic epithelial cells provide the microenvironment required for the expansion of T cells in the thymus, but their exact function is not well understood. Here, the authors report that thymic epithelial cells are the source of matricellular protein CYR61, which is involved in thymic function and T cell development.
- Yalin Emre
- , Magali Irla
- & Beat A. Imhof
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Article
| Open AccessPAD4 regulates proliferation of multipotent haematopoietic cells by controlling c-myc expression
Histone citrullination by peptidylarginine deiminase 4 (PAD4) regulates transcription but its physiological role is unclear. Here Nakashima et al. show that PAD4 controls proliferation of multipotent haematopoietic cells by modulating c-myc expression.
- Katsuhiko Nakashima
- , Satoko Arai
- & Toru Miyazaki
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Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote embryonic stem cell proliferation
Embryonic stem cells have a shortened cell cycle that allows for rapid proliferation, but the exact mechanisms are unclear. Here, a microRNA target, Trim71, is shown to inhibit the expression of a cyclin-dependent kinase inhibitor, thus enabling the G1–S phase cell cycle transition in embryonic stem cells.
- Hao-Ming Chang
- , Natalia J. Martinez
- & Richard I. Gregory
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In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo
In response to antigens, B cells proliferate and form germinal centres before differentiating into memory B cells or long-lived plasma cells. Here, a culture method is used to expand B cells in vitro, with the ability to shift the fate of the cells between memory B cells and long-lived plasma cells.
- Takuya Nojima
- , Kei Haniuda
- & Daisuke Kitamura
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Migration of growth factor-stimulated epithelial and endothelial cells depends on EGFR transactivation by ADAM17
Activation of the receptor tyrosine kinases FGFR2 and VEGFR2 results in ERK1/2 phosphorylation and cell migration. Here, the authors demonstrate that shedding of HB-EGF—a substrate of the metalloproteinase ADAM17—and activation of EGFR is required for FGFR2 and VEGFR2 mediated cell migration.
- Thorsten Maretzky
- , Astrid Evers
- & Carl P. Blobel