Ye-Guang Chen

Tsinghua University, Peping, Beijing, China

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Publications (106)820.11 Total impact

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    Full-text · Dataset · Jan 2016
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    Daniel J Klionsky · Kotb Abdelmohsen · Akihisa Abe · Md Joynal Abedin · Hagai Abeliovich · Abraham Acevedo Arozena · Hiroaki Adachi · Christopher M Adams · Peter D Adams · Khosrow Adeli · [...] · Xiao-Feng Zhu · Yuhua Zhu · Shi-Mei Zhuang · Xiaohong Zhuang · Elio Ziparo · Christos E Zois · Teresa Zoladek · Wei-Xing Zong · Antonio Zorzano · Susu M Zughaier ·
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    ABSTRACT: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.
    Full-text · Article · Jan 2016 · Autophagy
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    ABSTRACT: TGF-β is a pleiotropic cytokine that regulates a wide range of cellular actions and pathophysiological processes. TGF-β signaling is spatiotemporally fine-tuned. As a key negative regulator of TGF-β signaling, Smad7 exerts its inhibitory effects by blocking receptor activity, inducing receptor degradation or interfering with Smad-DNA binding. However, the functions and the molecular mechanisms underlying the actions of Smad7 in TGF-β signaling are still not fully understood. In this study we report a novel mechanism whereby Smad7 antagonizes TGF-β signaling at the Smad level. Smad7 oligomerized with R-Smad proteins upon TGF-β signaling and directly inhibited R-Smad activity, as assessed by Gal4-luciferase reporter assays. Mechanistically, Smad7 competes with Smad4 to associate with R-Smads and recruits the E3 ubiquitin ligase NEDD4L to activated R-Smads, leading to their polyubiquitination and proteasomal degradation. Similar to the R-Smad-Smad4 oligomerization, the interaction between R-Smads and Smad7 is mediated by their mad homology 2 (MH2) domains. A positive-charged basic region including the L3/β8 loop-strand module and adjacent amino acids in the MH2 domain of Smad7 is essential for the interaction. These results shed new light on the regulation of TGF-β signaling by Smad7.
    Full-text · Article · Jan 2016 · Journal of Biological Chemistry
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    Xiaohua Yan · Ye-Guang Chen
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    ABSTRACT: TGF-β is a prototype of the TGF-β cytokine superfamily and exerts multiple regulatory effects on cell activities. It signals through two types of membrane-bound serine/threonine kinase receptors. Upon TGF-β binding, the type II receptor TβRII recruits the type I receptor TβRI and form a functional heterocomplex. TβRII trans-phosphorylates the GS region of TβRI, thus triggering its kinase activity. Activated TβRI proceeds to activate downstream Smad2/3. Signal intensity and duration through the availability, activity and destiny of TGF-β receptors are finely controlled by multiple posttranslational modifications such as phosphorylation, ubiquitination, and neddylation. This chapter introduces methods for examination of these modifications of TGF-β receptors.
    Full-text · Article · Nov 2015 · Methods in molecular biology (Clifton, N.J.)
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    Gaoyang Zhu · Teng Fei · Zhongwei Li · Xiaohua Yan · Ye-Guang Chen
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    ABSTRACT: The development of a functional placenta is largely dependent upon proper proliferation and differentiation of trophoblast stem cells (TSCs). Activin signaling has long been regarded to play important roles during this process, but the exact mechanism is largely unknown. Here, we demonstrate that the X-chromosome gene BCL-6 corepressor (Bcor) is a critical downstream effector of activin to fine-tune mouse TSC fate decision. Bcor was specifically down-regulated by activin A in TSCs in a dose-dependent manner, and immediately up-regulated upon TSC differentiation. Knockdown of Bcor partially compensated the absence of activin A in maintaining the self-renewal of TSCs together with FGF4, while promoting syncytiotrophoblast differentiation in the absence of FGF4. Moreover, the impaired trophoblast giant cell and spongiotrophoblast differentiation upon Bcor knockdown also resembled the function of activin. Reporter analysis showed that BCOR inhibited the expression of the key trophoblast regulator genes Eomes and Cebpa by binding to their promoter regions. Our findings provide us a better understanding of placenta development and related diseases. Copyright © 2015, The American Society for Biochemistry and Molecular Biology.
    Full-text · Article · Jul 2015 · Journal of Biological Chemistry
  • Lu Wang · Ye-Guang Chen
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    ABSTRACT: Mesendoderm (ME) refers to the primitive streak in mammalian embryos, which has the ability to further differentiate into mesoderm and endoderm. A better understanding of the regulatory networks of mesendoderm differentiation of embryonic stem (ES) cells would provide important insights on early embryo patterning and a possible guidance for ES applications in regenerative medicine. Studies of developmental biology and embryology have offered a great deal of knowledge about key signaling pathways involved in primitive streak formation. Recently, various chemically-defined recipes have been formulated to induce differentiation of ES cells towards mesendoderm in vitro, which greatly facilitate the elucidation of the regulatory mechanisms of different signals involved in ME specification. Among the extrinsic signals, TGF-β/Activin signaling and Wnt signaling have been shown to be the most critical ones. On another side, intrinsic epigenetic regulation has been indicated to be important in ME determination. In this review, we summarize the current understanding of the extrinsic and intrinsic regulations of ES cells-to-ME differentiation and the crosstalk among them, aiming to get a general overview on ME specification and primitive streak formation. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Jun 2015 · Journal of Molecular Biology
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    ABSTRACT: Germ layer induction is one of the earliest events shortly after fertilization that initiates body formation of vertebrate embryos. In Xenopus, the maternally deposited transcriptional factor VegT promotes the expression of zygotic Nodal/Activin ligands that further form a morphogen gradient along the vegetal-animal axis and trigger the induction of the three germ layers. Here we found SCP3 (small C-terminal domain phosphatase 3) is maternally expressed and vegetally enriched in Xenopus embryos and is essential for the timely induction of germ layers. SCP3 is required for the full activation of Nodal/Activin and BMP signals and functions via dephosphorylation of linker regions of R-Smads. Consistently, the linker regions of R-Smads are heavily phosphorylated in fertilized eggs and this phosphorylation is gradually removed when embryos approach the midblastula transition (MBT). Knocking-down of maternal SCP3 attenuates these dephosphorylation events and the activation of Nodal/Activin and BMP signals after MBT. This study thus suggested that the maternal SCP3 serves as a vegetally enriched, intrinsic factor to ensure a prepared status of Smads for their activation by the upcoming ligands during germ layer induction of Xenopus embryos. Copyright © 2015, The American Society for Biochemistry and Molecular Biology.
    Full-text · Article · May 2015 · Journal of Biological Chemistry
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    ABSTRACT: Endocytosis and intracellular sorting of transforming growth factor-β (TGF-β) receptors play an important regulatory role in TGF-β signaling. Two major endocytic pathways, clathrin- and caveolae-mediated endocytosis, have been reported to independently mediate the internalization of TGF-β receptors. In this study, we demonstrate that the clathrin- and caveolae-mediated endocytic pathways can converge during TGF-β receptor endocytic trafficking. By tracking the intracellular dynamics of fluorescently-labeled TGF-β type I receptor (TβRI), we found that after mediating TβRI internalization, certain clathrin-coated vesicles and caveolar vesicles are fused underneath the plasma membrane, forming a novel type of caveolin-1 and clathrin double-positive vesicles. Under the regulation of Rab5, the fused vesicles are targeted to early endosomes and thus deliver the internalized TβRI to the caveolin-1 and EEA1 double-positive early endosomes (caveolin-1-positive early endosomes). We further showed that the caveolin-1-positive early endosomes are positive for Smad3/SARA, Rab11 and Smad7/Smurf2, and may act as a multifunctional device for TGF-β signaling and TGF-β receptor recycling and degradation. Therefore, these findings uncover a novel scenario of endocytosis, the direct fusion of clathrin-coated and caveolae vesicles during TGF-β receptor endocytic trafficking, which leads to the formation of the multifunctional sorting device, caveolin-1-positive early endosomes, for TGF-β receptors.Cell Research advance online publication 22 May 2015; doi:10.1038/cr.2015.60.
    Full-text · Article · May 2015 · Cell Research
  • Bing Zhao · Zhen Qi · Yehua Li · Chongkai Wang · Wei Fu · Ye-Guang Chen
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    ABSTRACT: Lgr5+ stem cells are crucial to gut epithelium homeostasis, and therapies targeting these cells hold promise for treatment of gastrointestinal diseases. Here we report that the non-muscle-myosin-II (NMII) heavy chain Myh9 accumulates at epithelial injury sites in mice distal colon treated with dextran sulphate sodium (DSS). Gut-epithelium-specific Myh9 monoallelic deletion alleviates DSS-induced colonic crypt damage and acute colitis. Consistently, the NMII inhibitor blebbistatin can improve the survival of Lgr5+ stem cells and the growth of Lgr5 organoids. Mechanistically, inhibition of NMII by blebbistatin or Myh9 monoallelic deletion activates Akt through Rac1 and PAK1, which is essential for the survival and pluripotency of Lgr5+ cells. These results establish a critical role of the Myh9-Rac1-PAK1-Akt pathway in the maintenance of Lgr5+ stem cells. As blebbistatin can mitigate DSS-induced colitis and preserve Lgr5+ colonic stem cells in vivo, our findings provide a potential therapeutic intervention of gastrointestinal epithelium injury and degenerative diseases.
    No preview · Article · May 2015 · Nature Communications
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    Zhen Qi · Ye-Guang Chen
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    ABSTRACT: The remarkable ability of rapid self-renewal makes the intestinal epithelium an ideal model for the study of adult stem cells. The intestinal epithelium is organized into villus and crypt, and a group of intestinal stem cells located at the base of crypt are responsible for this constant self-renewal throughout the life. Identification of the intestinal stem cell marker Lgr5, isolation and in vitro culture of Lgr5+ intestinal stem cells and the use of transgenic mouse models have significantly facilitated the studies of intestinal stem cell homeostasis and differentiation, therefore greatly expanding our knowledge of the regulatory mechanisms underlying the intestinal stem cell fate determination. In this review, we summarize the current understanding of how signals of Wnt, BMP, Notch and EGF in the stem cell niche modulate the intestinal stem cell fate.
    Full-text · Article · May 2015 · Science China. Life sciences
  • Benyu Ma · Bofeng Liu · Weipeng Cao · Chan Gao · Zhen Qi · Yuanheng Ning · Ye-Guang Chen
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    ABSTRACT: Autophagy is a regulated process that sequesters and transports cytoplasmic materials such as protein aggregates via autophagosomes to lysosomes for degradation. Dapper1 (Dpr1), an interacting protein of Dishevelled (Dvl), antagonizes Wnt signaling by promoting Dvl degradation via lysosomes. However, the mechanism is unclear. Here, we show that Dpr1 promotes the Von Hippel-Lindau tumor suppressor (VHL)-mediated ubiquitination of Dvl2 and its autophagic degradation. Knockdown of Dpr1 decreases the interaction between Dvl2 and pVHL, resulting in reduced ubiquitination of Dvl2. Dpr1-mediated autophagic degradation of Dvl2 depends on Dvl2 aggregation. Moreover, the aggregate-prone proteins Dvl2, p62 and the hungtingtin mutant Htt103Q promote autophagy in a Dpr1-dependent manner. These protein aggregates enhance the Beclin1-Vps34 interaction and Atg14L puncta formation, indicating that aggregated proteins stimulate autophagy initiation. Ubiquitination is not essential for the aggregates-induced autophagy initiation as inhibition of the ubiquitin-activation E1 enzyme activity did not block the aggregates-induced Atg14L puncta formation. Our findings suggest that Dpr1 promotes the ubiquitination of Dvl2 by pVHL and mediates the protein aggregates-elicited autophagy initiation. Copyright © 2015, The American Society for Biochemistry and Molecular Biology.
    No preview · Article · Mar 2015 · Journal of Biological Chemistry
  • Jun Du · Senlian Hong · Lu Dong · Bo Cheng · Liang Lin · Bing Zhao · Ye-Guang Chen · Xing Chen
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    ABSTRACT: Epithelial-mesenchymal transition (EMT) is a fundamental process in embryonic development and organ formation. Aberrant regulation of EMT often leads to tumor progression. Changes in cell-surface sialylation have recently been implicated in mediating EMT. Herein we report the visualization of dynamic changes of sialylation and glycoproteomic analysis of newly synthesized sialylated proteins in EMT by metabolic labeling of sialylated glycans with azides, followed by click-labeling with fluorophores and affinity tags. We discovered that sialylation was downregulated during EMT, but then reverted and upregulated in the mesenchymal state after EMT, accompanied by mRNA expression level changes of genes involved in the sialic acid biosynthesis. Quantitative proteomic analysis identified a list of sialylated proteins whose biosynthesis was dynamically regulated during EMT. Sialylation of cell-surface adherent receptor integrin β4 was found to be downregulated, which may regulate integrin functions during EMT. Furthermore, a global sialylation inhibitor was used to probe the functional role of sialylation during EMT. We found that inhibition of sialylation promoted EMT. Taken together, our findings suggest the important role of sialylation in regulating EMT and imply its possible function in related pathophysiological events, such as cancer metastasis. Copyright © 2015, The American Society for Biochemistry and Molecular Biology.
    No preview · Article · Mar 2015 · Journal of Biological Chemistry
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    ABSTRACT: Receptor-mediated signal transduction modulates complex cellular behaviours such as cell growth, migration and differentiation. Although photoactivatable proteins have emerged as a powerful tool for controlling molecular interactions and signalling cascades at precise times and spaces using light, many of these light-sensitive proteins are activated by ultraviolent or visible light, which has limited tissue penetration. Here, we report a single-walled carbon nanotube (SWCNT)-assisted approach that enables near-infrared light-triggered activation of transforming growth factor β (TGF-β) signal transduction, an important signalling pathway in embryonic development and cancer progression. The protein complex of TGF-β and its latency-associated peptide is conjugated onto SWCNTs, where TGF-β is inactive. Upon near-infrared irradiation, TGF-β is released through the photothermal effect of SWCNTs and becomes active. The released TGF-β activates downstream signal transduction in live cells and modulates cellular behaviours. Furthermore, preliminary studies show that the method can be used to mediate TGF-β signalling in living mice.
    Full-text · Article · Mar 2015 · Nature Nanotechnology
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    Yongsheng Huang · Peng Wang · Hua Chen · Yi Ding · Ye-Guang Chen
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    ABSTRACT: Wnt signaling regulates embryonic development and tissue homeostasis by modulating cell proliferation, differentiation and migration. Dapper1 (Dpr1) has been shown to be an important key negative regulator of Wnt signaling by promoting Dishevelled (Dvl) degradation. In this study, we report that Myc-interacting zinc-finger protein 1 (MIZ1) interacts with Dpr1, and this interaction attenuates the ability of Dpr1 to induce Dvl2 degradation, thus enhancing Wnt signaling. Mechanistically, MIZ1 is translocated from the nucleus to the cytoplasm upon Wnt3a stimulation or over-expression of Dpr1 and Dvl2, disrupting the interaction between Dpr1 and Dvl2. Furthermore, MIZ1 can promote the proliferation of breast cancer MDA-MB-231 and BT-549 cells through Wnt signaling and reverse the anti-proliferative effect of Dpr1 on colorectal cancer Caco-2. Together, our findings establish a novel layer of Wnt signaling regulation via the MIZ1-Dpr1-Dvl axis.
    Full-text · Article · Jan 2015 · Biochemical Journal
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    Wangxi Luo · Tie Xia · Li Xu · Ye-Guang Chen · Xiaohong Fang
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    ABSTRACT: Transforming growth factor β receptor II (Tβ RII) is synthesized in the cytoplasm and then transported to the plasma membrane of cells to fulfil its signalling duty. Here, we applied live-cell fluorescence imaging techniques, in particular quasi-total internal reflection fluorescence microscopy, to imaging fluorescent protein-tagged Tβ RII and monitoring its secretion process. We observed punctuate-like Tβ RII-containing post-Golgi vesicles formed in MCF7 cells. Single-particle tracking showed that these vesicles travelled along the microtubules at an average speed of 0.51 μm/s. When stimulated by TGF-β ligand, these receptor-containing vesicles intended to move towards the plasma membrane. We also identified several factors that could inhibit the formation of such post-Golgi vesicles. Although the inhibitory mechanisms still remain unknown, the observed characteristics of Tβ RII-containing vesicles provide new information on intracellular Tβ RII transportation. It also renders Tβ RII a good model system for studying post-Golgi vesicle-trafficking and protein transportation. (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).
    Full-text · Article · Oct 2014 · Journal of Biophotonics
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    Bing Zhao · Ye-Guang Chen
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    ABSTRACT: Transforming growth factor-β (TGF-β) signaling regulates diverse cellular processes, including cell proliferation, differentiation, apoptosis, cell plasticity, and migration. TGF-β signaling can be mediated by Smad proteins or other signaling proteins such as MAP kinases and Akt. TGF-β signaling is tightly regulated at different levels along the pathways to ensure its proper physiological functions in different cells and tissues. Deregulation of TGF-β signaling has been associated with various kinds of diseases, such as cancer and tissue fibrosis. This paper focuses on our recent work on regulation of TGF-β signaling.
    Preview · Article · Sep 2014
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    ABSTRACT: Wnt/β-catenin signaling via the β-catenin/TCF complex plays crucial roles in tissue homeostasis. Wnt stimulated β-catenin/TCF complex accumulation in the nucleus regulates cell survival, proliferation, and differentiation through the transcription of target genes. Compared with those in G1, LRP6 receptor activation and cytosolic β-catenin are both up-regulated in G2 cells. However, accumulation of the Wnt pathway negative regulator, AXIN2, also occurs in this phase. Therefore, it is unclear whether Wnt signaling is active in G2 phase cells. Here, we established a bimolecular fluorescence complementation (BiFC) biosensor system for the direct visualization of β-catenin/TCF interaction in living cells. Using the BiFC biosensor and co-immunoprecipitation experiments, we demonstrated the nucleus-localized β-catenin/TCF complex increases during the S and G2 phases, and declines in the next G1 phase. Accordingly, a subset of Wnt target genes was transcribed by the β-catenin/TCF complex during both S and G2 phases. In contrast, transient inhibition of this complex disturbed both cell survival and G2/M progression. Our results suggest that in S-G2 phase cells, Wnt/β-catenin signaling is highly active and functions to ensure cell survival and cell-cycle progression.
    Full-text · Article · Sep 2014 · Journal of Cell Science
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    ABSTRACT: Autophagy is an intracellular degradation process to clear up aggregated proteins or aged and damaged organelles. The Beclin1-Vps34-Atg14L complex is essential for autophagosome formation. However, how the complex formation is regulated is unclear. Here, we show that Dapper1 (Dpr1) acts as a critical regulator of the Beclin1-Vps34-Atg14L complex to promote autophagy. Dpr1 ablation in the central nervous system results in motor coordination defect and accumulation of p62 and ubiquitinated proteins. Dpr1 increases autophagosome formation as indicated by elevated puncta formation of LC3, Atg14L and DFCP1 (Double FYVE-containing protein 1). Conversely, loss of Dpr1 impairs LC3 lipidation and causes p62/SQSTM1 accumulation. Dpr1 directly interacts with Beclin1 and Atg14L and enhances the Beclin1-Vps34 interaction and Vps34 activity. Together, our findings suggest that Dpr1 enhances the Atg14L-Beclin1-Vps34 complex formation to drive autophagy.Cell Research advance online publication 1 July 2014; doi:10.1038/cr.2014.84.
    Full-text · Article · Jul 2014 · Cell Research
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    ABSTRACT: Development of animal embryos before zygotic genome activation at the midblastula transition (MBT) is essentially supported by egg-derived maternal products. Nodal proteins are crucial signals for mesoderm and endoderm induction after the MBT. It remains unclear which maternal factors activate zygotic expression of nodal genes in the ventrolateral blastodermal margin of the zebrafish blastulas. In this study, we show that loss of maternal Eomesodermin a (Eomesa), a T-box transcription factor, impairs zygotic expression of the nodal genes ndr1 and ndr2 as well as mesodermal and endodermal markers, indicating an involvement in mesendoderm induction. Maternal Eomesa is also required for timely zygotic expression of the transcription factor gene mxtx2, a regulator of nodal gene expression. Eomesa directly binds to the Eomes-binding sites in the promoter or enhancer of ndr1, ndr2, and mxtx2 to activate their transcription. Furthermore, human and mouse Nodal genes are also regulated by Eomes. Transfection of zebrafish eomesa into murine embryonic stem cells promotes mesendodermal differentiation with constant higher levels of endogenous Nodal expression, suggesting a conserved function of Eomes. Taken together, our findings reveal a conserved role of maternal T-box transcription factors in regulating nodal gene expression and mesendoderm induction in vertebrate embryos.
    Full-text · Article · Jun 2014 · Journal of Molecular Cell Biology
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    Yan Zhang · Yi Ding · Ye-Guang Chen · Qinghua Tao
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    ABSTRACT: During the early vertebrate body plan formation, convergent extension (CE) of dorsal mesoderm and neurectoderm is coordinated by the evolutionarily conserved non-canonical Wnt/PCP signaling. Dishevelled (Dvl), a key mediator of Wnt/PCP signaling, is essential for the medial-lateral polarity formation in the cells undergoing convergent extension movements. NEDD4L, a highly conserved HECT type E3 ligase, has been reported to regulate the stability of multiple substrates including Dvl2. Here we demonstrate that NEDD4L is required for the cellular polarity formation and convergent extension in the early Xenopus embryos. Depletion of NEDD4L in early Xenopus embryos results in the loss of mediolateral polarity of the convergent-extending mesoderm cells and the shortened body axis, resembling those defects caused by the disruption of non-canonical Wnt signaling. Depletion of xNEDD4L also blocks the elongation of the animal explants in response to endogenous mesoderm inducing signals and partially compromises the expression of Brachyury. Importantly, reducing Dvl2 expression can largely rescue the cellular polarity and convergent extension defects in NEDD4L-depleted embryos and explants. Together with the data that NEDD4L reduces Dvl2 protein expression in the frog embryos, our findings suggest that regulation of Dvl protein levels by NEDD4L is essential for convergent extension during early Xenopus embryogenesis.
    Preview · Article · May 2014 · Developmental Biology

Publication Stats

5k Citations
820.11 Total Impact Points

Institutions

  • 2004-2015
    • Tsinghua University
      • School of Life Sciences
      Peping, Beijing, China
  • 2012
    • University of Michigan
      • Life Sciences Institute
      Ann Arbor, MI, United States
  • 2007
    • National Tsing Hua University
      Hsin-chu-hsien, Taiwan, Taiwan
    • Baylor College of Medicine
      • Department of Molecular & Cellular Biology
      Houston, Texas, United States
  • 2002-2003
    • University of California, Riverside
      • Division of Biomedical Sciences
      Riverside, CA, United States