Abstract:
:Epithelial-mesenchymal transition (EMT) enables cells to gain migratory and invasive features underlined by major transcriptional and epigenetic reprogramming. However, most studies have focused on the endpoints of the EMT process, and the epistatic hierarchy of the transcriptional networks underlying EMT has remained elusive. We have used a siRNA-based, functional high-content microscopy screen to identify 46 (co)transcription factors ((co)TFs) and 13 miRNAs critically required for EMT in normal murine mammary gland (NMuMG) cells. We compared dynamic gene expression during EMT kinetics and used functional perturbation of critical (co)TFs and miRNAs to identify groups and networks of EMT genes. Computational analysis as well as functional validation experiments revealed interaction networks between TFs and miRNAs and delineated the hierarchical and functional interactions of multiple EMT regulatory networks in NMuMG cells.
journal_name
Dev Celljournal_title
Developmental cellauthors
Meyer-Schaller N,Cardner M,Diepenbruck M,Saxena M,Tiede S,Lüönd F,Ivanek R,Beerenwinkel N,Christofori Gdoi
10.1016/j.devcel.2018.12.023subject
Has Abstractpub_date
2019-02-25 00:00:00pages
539-553.e6issue
4eissn
1534-5807issn
1878-1551pii
S1534-5807(18)31123-7journal_volume
48pub_type
杂志文章abstract::Smad4 is a central intracellular effector of TGF-beta signaling. Smad-independent TGF-beta pathways, such as those mediated by p38 MAPK, have been identified in cell culture systems, but their in vivo functional mechanisms remain unclear. In this study, we investigated the role of TGF-beta signaling in tooth and palat...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2008.06.004
更新日期:2008-08-01 00:00:00
abstract::Odorant receptors (ORs) in the olfactory epithelium bind to volatile small molecules leading to the perception of smell. ORs are expressed in many tissues but their functions are largely unknown. We show multiple ORs display distinct mRNA expression patterns during myogenesis in vitro and muscle regeneration in vivo. ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2009.09.004
更新日期:2009-11-01 00:00:00
abstract::Merlin encoded by the Nf2 gene is a bona fide tumor suppressor that has been implicated in regulation of both the Hippo-Yap and Rac1-Pak1 pathways. Using genetically engineered murine liver models, we show that co-deletion of Rac1 with Nf2 blocks tumor initiation but paradoxically exacerbates hepatomegaly induced by N...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2016.09.027
更新日期:2016-11-21 00:00:00
abstract::The role of mitochondria in Drosophila programmed cell death remains unclear, although certain gene products that regulate cell death seem to be evolutionarily conserved. We find that developmental programmed cell death stimuli in vivo and multiple apoptotic stimuli ex vivo induce dramatic mitochondrial fragmentation ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2007.02.002
更新日期:2007-05-01 00:00:00
abstract::Blood vessels form an important interface between the environment and the organism by carrying oxygen and nutrients to all cells and thus determining cellular metabolism. It is therefore not surprising that oxygen and metabolism influence the development of the vascular network. Here, we discuss recent insights regard...
journal_title:Developmental cell
pub_type: 杂志文章,评审
doi:10.1016/j.devcel.2009.01.003
更新日期:2009-02-01 00:00:00
abstract::The cytoplasm is not a homogenous solution but instead consists of large dynamic assemblies that arise from transient molecular interactions. Some of these structures have been shown to represent liquid droplets of concentrated protein and RNA. Liquid phase separation of cytoplasm may be a fundamental principle of cyt...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2011.06.013
更新日期:2011-07-19 00:00:00
abstract::In Drosophila, left/right (LR) asymmetry is apparent in the directional looping of the gut and male genitalia. The dextral orientation of the organs depends on the activity of a single gene, MyosinID (myoID), whose mutation leads to a fully inverted LR axis, thus revealing the activity of a recessive sinistral pathway...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2012.11.013
更新日期:2013-01-14 00:00:00
abstract::Metastasizing breast carcinoma cells have been hypothesized to mobilize tissue-invasive activity by co-opting the proteolytic systems employed by normal mammary epithelial cells undergoing branching morphogenesis. However, the critical effectors underlying morphogenesis remain unidentified, and their relationship to b...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2018.08.025
更新日期:2018-10-22 00:00:00
abstract::Numerous signals drive the proliferative expansion of the distal endoderm and the underlying mesenchyme during lung branching morphogenesis, but little is known about how these signals are integrated. Here, we show by analysis of conditional double mutants that the two T-box transcription factor genes Tbx2 and Tbx3 ac...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2016.08.007
更新日期:2016-10-24 00:00:00
abstract::Centromeres are essential for accurate chromosome segregation and are marked by centromere protein A (CENP-A) nucleosomes. Mis-targeted CENP-A chromatin has been shown to seed centromeres at non-centromeric DNA. However, the requirements for such de novo centromere formation and transmission in vivo remain unknown. He...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2020.01.005
更新日期:2020-02-10 00:00:00
abstract::The E-Cadherin-catenin complex plays a critical role in epithelial cell-cell adhesion, polarization, and morphogenesis. Here, we have analyzed the mechanism of Drosophila E-Cadherin (DE-Cad) localization. Loss of function of the Drosophila exocyst components sec5, sec6, and sec15 in epithelial cells results in DE-Cad ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2005.07.013
更新日期:2005-09-01 00:00:00
abstract::Many promoters in eukaryotes have nucleosome-depleted regions (NDRs) containing transcription factor binding sites. However, the functional significance of NDRs is not well understood. Here, we examine NDR function in two cell cycle-regulated promoters, CLN2pr and HOpr, by varying nucleosomal coverage of the binding s...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2010.02.007
更新日期:2010-04-20 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::Passenger proteins migrate from inner centromeres to the spindle midzone during late mitosis, and those described to date are essential both for proper chromosome segregation and for completion of cell cleavage. We have purified and cloned the human passenger protein TD-60, and we here report that it is a member of th...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/s1534-5807(03)00205-3
更新日期:2003-08-01 00:00:00
abstract::Although autophagy is being pursued as a therapeutic target in clinical oncology trials, its effects on metastasis, the principal cause of cancer mortality, remain unclear. Here, we utilize mammary cancer models to temporally delete essential autophagy regulators during carcinoma progression. Though genetic ablation o...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2020.01.025
更新日期:2020-03-09 00:00:00
abstract::Cells commit to mitosis by abruptly activating the mitotic cyclin-Cdk complexes. During Drosophila gastrulation, mitosis is associated with the transcriptional activation of cdc25(string), a phosphatase that activates Cdk1. Here, we demonstrate that the switch-like entry into mitosis observed in the Drosophila embryo ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2012.01.019
更新日期:2012-04-17 00:00:00
abstract::FGF/ERK signaling is crucial for the patterning and proliferation of cell lineages that comprise the mouse blastocyst. However, ERK signaling dynamics have never been directly visualized in live embryos. To address whether differential signaling is associated with particular cell fates and states, we generated a targe...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2020.09.030
更新日期:2020-11-09 00:00:00
abstract::Actomyosin flows are involved in a variety of cellular processes, including cytokinesis, cell migration, polarization, and morphogenesis. In epithelia, flow polarization orients cell deformations. It is unclear, however, how flows are polarized and how global patterns of junction remodeling emerge from flow polarizati...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2013.06.020
更新日期:2013-07-29 00:00:00
abstract::Large intergenic noncoding (linc) RNAs constitute a new dimension of posttranscriptional gene regulation. In this issue of Developmental Cell, Wang et al. (2013) find that linc-RoR maintains human embryonic stem cell self-renewal by functioning as a sponge to trap miR-145, thus regulating core pluripotency factors Oct...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2013.03.020
更新日期:2013-04-15 00:00:00
abstract::Fission yeast Pat1 kinase inhibits sexual differentiation by phosphorylating the meiotic inducer Mei2 and the transcription factor Ste11. Here, we show how Pat1 downregulates these proteins. Mei2 is degraded via a ubiquitin-proteasome pathway in a phosphorylation-dependent fashion. The E2 Ubc2 and the E3 Ubr1 are requ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/s1534-5807(01)00037-5
更新日期:2001-09-01 00:00:00
abstract::Human centromeres are defined by alpha satellite DNA arrays that are distinct and chromosome specific. Most human chromosomes contain multiple alpha satellite arrays that are competent for centromere assembly. Here, we show that human centromeres are defined by chromosome-specific RNAs linked to underlying organizatio...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2017.07.001
更新日期:2017-08-07 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
更新日期:2014-04-28 00:00:00
abstract::Hedgehog (Hh) signaling during development and in postembryonic tissues requires activation of the 7TM oncoprotein Smoothened (Smo) by mechanisms that may involve endogenous lipidic modulators. Exogenous Smo ligands previously identified include the plant sterol cyclopamine (and its therapeutically useful synthetic mi...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2013.07.015
更新日期:2013-08-26 00:00:00
abstract::The faithful alignment of homologous chromosomes during meiotic prophase requires the coordination of DNA double-strand break (DSB) repair with large-scale chromosome reorganization. Here we identify the phosphatase PP4 (Pph3/Psy2) as a mediator of this process in Saccharomyces cerevisiae. In pp4 mutants, early stages...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2010.09.006
更新日期:2010-10-19 00:00:00
abstract::Asymmetric cell divisions generate cellular diversity. In Drosophila, embryonic neuroblasts target cell fate determinants basally, rotate their spindles by 90 degrees to align with the apical-basal axis, and divide asymmetrically in a stem cell-like fashion. In this process, apically localized Bazooka recruits Inscute...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/s1534-5807(03)00020-0
更新日期:2003-02-01 00:00:00
abstract::Drosophila proprioceptors (chordotonal organs) are structured as a linear array of four lineage-related cells: a neuron, a glial cell, and two accessory cells, called cap and ligament, between which the neuron is stretched. To function properly as stretch receptors, chordotonal organs must be stably anchored at both e...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2004.07.001
更新日期:2004-08-01 00:00:00
abstract::RITS (RNA-induced initiation of transcriptional gene silencing complex) plays diverse roles in heterochromatin regulation: silencing transcription by recruitment of chromatin modifiers and destroying transcripts by RNAi. In a recent issue of Molecular Cell, Li et al. now show that the polymerization of Tas3, a compone...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2009.05.002
更新日期:2009-05-01 00:00:00
abstract::Changes in the genetic makeup of an organism can extend lifespan significantly if they promote tolerance to environmental insults and thus prevent the general deterioration of cellular function that is associated with aging. Here, we introduce the Jun N-terminal kinase (JNK) signaling pathway as a genetic determinant ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/s1534-5807(03)00323-x
更新日期:2003-11-01 00:00:00
abstract::How metabolism is rewired during embryonic development is still largely unknown, as it remains a major technical challenge to resolve metabolic activities or metabolite levels with spatiotemporal resolution. Here, we investigated metabolic changes during development of organogenesis-stage mouse embryos, focusing on th...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2017.01.015
更新日期:2017-02-27 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