Abstract:
:Little is known about the mechanisms governing neonatal growth and maturation of organs. Here we demonstrate that calcineurin/Nuclear Factor of Activated T cells (Cn/NFAT) signaling regulates neonatal pancreatic development in mouse and human islets. Inactivation of calcineurin b1 (Cnb1) in mouse islets impaired dense core granule biogenesis, decreased insulin secretion, and reduced cell proliferation and mass, culminating in lethal diabetes. Pancreatic β cells lacking Cnb1 failed to express genes revealed to be direct NFAT targets required for replication, insulin storage, and secretion. In contrast, glucokinase activation stimulated Cn-dependent expression of these genes. Calcineurin inhibitors, such as tacrolimus, used for human immunosuppression, induce diabetes. Tacrolimus exposure reduced Cn/NFAT-dependent expression of factors essential for insulin dense core granule formation and secretion and neonatal β cell proliferation, consistent with our genetic studies. Discovery of conserved pathways regulating β cell maturation and proliferation suggests new strategies for controlling β cell growth or replacement in human islet diseases.
journal_name
Dev Celljournal_title
Developmental cellauthors
Goodyer WR,Gu X,Liu Y,Bottino R,Crabtree GR,Kim SKdoi
10.1016/j.devcel.2012.05.014subject
Has Abstractpub_date
2012-07-17 00:00:00pages
21-34issue
1eissn
1534-5807issn
1878-1551pii
S1534-5807(12)00241-9journal_volume
23pub_type
杂志文章abstract::COPII vesicles assemble at ER subdomains called transitional ER (tER) sites, but the mechanism that generates tER sites is unknown. To study tER biogenesis, we analyzed the transmembrane protein Sec12, which initiates COPII vesicle formation. Sec12 is concentrated at discrete tER sites in the budding yeast Pichia past...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/s1534-5807(04)00129-7
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abstract::In a recent issue of Molecular Cell, Cairo et al. (2013) report that the spindle checkpoint protein Mad1 shuttles between unattached kinetochores and nuclear pores. Mobile Mad1 inhibits the import receptor Kap121p, thus indirectly changing spindle dynamics. This adds nuclear transport control to the mitotic roles of M...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2013.01.003
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abstract::Neutrophils, in response to a chemoattractant gradient, undergo dynamic F-actin remodeling, a process important for their directional migration or chemotaxis. However, signaling mechanisms for chemoattractants to regulate the process are incompletely understood. Here, we characterized chemoattractant-activated signali...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2011.10.023
更新日期:2011-12-13 00:00:00
abstract::Reporting in Developmental Cell, Pereira et al. (2016) use in vitro lineage reprogramming insights to inform understanding of hematopoietic stem cell (HSC) development in vivo. They find Prom1(+)Sca1(+)CD34(+)CD45(-) hemogenic precursors, akin to fibroblast-derived hemato-vascular precursors, in mouse placenta and emb...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2016.02.022
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abstract::Cytokinins affect plant immunity to various pathogens; however, the mechanisms coupling plant-derived cytokinins to pathogen responses have been elusive. Here, we found that plant-derived cytokinins promote resistance of Arabidopsis to Pseudomonas syringae pv. tomato DC3000 (Pst). Modulated cytokinin levels or signali...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2010.07.011
更新日期:2010-08-17 00:00:00
abstract::Dynamic rearrangements of the actin cytoskeleton play a key role in numerous cellular processes. In Drosophila, fusion between a muscle founder cell and a fusion competent myoblast (FCM) is mediated by an invasive, F-actin-enriched podosome-like structure (PLS). Here, we show that the dynamics of the PLS is controlled...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2011.04.007
更新日期:2011-05-17 00:00:00
abstract::Initiation of DNA replication must be restricted to occur only once per cell cycle. In most bacteria, DnaA protein binds replication origins and promotes the initiation of DNA replication. We have found that in Bacillus subtilis, DnaA only colocalizes with origin regions at early or late stages of the cell cycle, when...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2008.09.010
更新日期:2008-12-01 00:00:00
abstract::The generation and shedding of extracellular vesicles (EVs), including exosomes and microvesicles (MVs), by cells has emerged as a form of intercellular communication with important roles in several physiological processes and diseases such as cancer. These membrane-enclosed packets can transfer specific proteins, RNA...
journal_title:Developmental cell
pub_type: 杂志文章,评审
doi:10.1016/j.devcel.2016.04.019
更新日期:2016-05-23 00:00:00
abstract::Auxins are a class of phytohormones implicated in virtually every aspect of plant growth and development. Many early plant responses to auxin are apparently mediated by members of a family of Aux/IAA proteins that dimerize with and inhibit members of the auxin response factor (ARF) family of transcription factors. Aux...
journal_title:Developmental cell
pub_type: 杂志文章,评审
doi:10.1016/s1534-5807(01)00077-6
更新日期:2001-11-01 00:00:00
abstract::Exposure to environmental teratogenic pollutant leads to severe birth defects. However, the biological events underlying these developmental abnormalities remain undefined. Here, we report a molecular link between an environmental stress response pathway and key developmental genes during craniofacial development. Str...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2015.02.006
更新日期:2015-04-06 00:00:00
abstract::Cell polarity plays a key role in the development of the central nervous system (CNS). Interestingly, disruption of cell polarity is seen in many cancers. ASPP2 is a haplo-insufficient tumor suppressor and an activator of the p53 family. In this study, we show that ASPP2 controls the polarity and proliferation of neur...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2010.06.003
更新日期:2010-07-20 00:00:00
abstract::The extracellular signals and corresponding receptors that align the mitotic spindle of symmetrically dividing cells within an epithelial sheet are largely unknown. In this issue of Developmental Cell, Xia et al. (2015) identify semaphorin-plexin signaling as a regulator of spindle orientation critical for kidney deve...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2015.04.012
更新日期:2015-05-04 00:00:00
abstract::Unravelling the role of cytoskeleton regulators may be complicated by adaptations to experimental manipulations. In this issue of Developmental Cell, Cerikan et al. (2016) reveal how acute effects of DOCK6 RhoGEF depletion on RAC1 and CDC42 activation are reversed over time by compensatory mechanisms that re-establish...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2016.09.020
更新日期:2016-10-10 00:00:00
abstract::Exposing cells to folding stress causes a subset of their proteins to misfold and accumulate in inclusion bodies (IBs). IB formation and clearance are both active processes, but little is known about their mechanism. To shed light on this issue, we performed a screen with over 4,000 fluorescently tagged yeast proteins...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2015.04.015
更新日期:2015-06-08 00:00:00
abstract::Vertebrate hematopoiesis first produces primitive (embryonic) lineages and ultimately generates the definitive (adult) blood. Whereas definitive hematopoiesis may produce many diverse blood types via a common multipotent progenitor, primitive hematopoiesis has been thought to produce only erythrocytes or macrophages v...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2009.04.007
更新日期:2009-05-01 00:00:00
abstract::The extracellular matrix (ECM) plays a major role in cancer progression through its increased deposition and alignment. In this issue of Developmental Cell, Fattet et al. reveal a pathway in which ECM stiffness promotes EPHA2/LYN complex activation, leading to TWIST1 nuclear localization and triggering EMT in breast c...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2020.06.032
更新日期:2020-08-10 00:00:00
abstract::MicroRNAs are important regulators of normal and malignant hematopoiesis. A paper by Lu et al. in this issue of Developmental Cell demonstrates how one microRNA, miR-150, plays a critical role in commitment of the erythroid-megakaryocyte progenitor by modulating the level of the widely expressed transcription factor M...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2008.05.011
更新日期:2008-06-01 00:00:00
abstract::In a recent issue of Nature, Bohnert and Kenyon (2017) describe a signaling pathway that prevents transgenerational inheritance of cytoplasmic protein aggregates. Fertilizing sperm trigger aggregate clearance in the ovum by a microautophagy-like effector mechanism mediated by inter-organelle communication between lyso...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2017.12.016
更新日期:2018-01-08 00:00:00
abstract::Novel body structures are often generated by the redeployment of ancestral components of the genome. In this issue of Developmental Cell, Glassford et al. (2015) present a thorough analysis of the co-option of a gene regulatory network in the origin of an evolutionary novelty. ...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2015.08.022
更新日期:2015-09-14 00:00:00
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journal_title:Developmental cell
pub_type: 杂志文章,评审
doi:10.1016/s1534-5807(02)00374-x
更新日期:2002-12-01 00:00:00
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journal_title:Developmental cell
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doi:10.1016/s1534-5807(02)00260-5
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journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2016.02.010
更新日期:2016-03-07 00:00:00
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journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2015.06.015
更新日期:2015-08-24 00:00:00
abstract::Autophagy is the major cellular process responsible for bulk cytoplasmic degradation. Two reports in this issue of Developmental Cell describe how both PI3 kinase and TOR signaling in Drosophila are critical for controlling autophagy in response to developmental and environmental cues. ...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2004.07.014
更新日期:2004-08-01 00:00:00
abstract::The Ras/PI3K/extracellular signal-regulated kinases (ERK) signaling network plays fundamental roles in cell growth, survival, and migration and is frequently activated in cancer. Here, we show that the activities of the signaling network propagate as coordinated waves, biased by growth factor, which drive actin-based ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2020.08.001
更新日期:2020-09-14 00:00:00
abstract::We show that Rap2, a member of the Ras GTPase family, positively regulates Activin/Nodal signaling activity by controlling the trafficking of its receptors. In the absence of ligand activation, Rap2 directs internalized Activin/Nodal receptors into a recycling pathway, thereby preventing their degradation and maintain...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2008.05.004
更新日期:2008-07-01 00:00:00
abstract::The emergence of limb-driven locomotor behaviors was a key event in the evolution of vertebrates and fostered the transition from aquatic to terrestrial life. We show that the generation of limb-projecting lateral motor column (LMC) neurons in mice relies on a transcriptional autoregulatory module initiated via transi...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2014.03.008
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abstract::The chemokine CXCL12 and its receptor CXCR4 have many functions during embryonic and post-natal life. We used murine models to investigate the role of CXCL12/CXCR4 signaling in cardiac development and found that embryonic Cxcl12-null hearts lacked intra-ventricular coronary arteries (CAs) and exhibited absent or mispl...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2015.03.026
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journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2017.02.025
更新日期:2017-03-13 00:00:00
abstract::The mTOR kinase controls cell growth, proliferation, and survival through two distinct multiprotein complexes, mTORC1 and mTORC2. mTOR and mLST8 are in both complexes, while raptor and rictor are part of only mTORC1 and mTORC2, respectively. To investigate mTORC1 and mTORC2 function in vivo, we generated mice deficien...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2006.10.007
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