Conversion of an extracellular Dpp/BMP morphogen gradient into an inverse transcriptional gradient.

Abstract:

:Morphogen gradients control body pattern by differentially regulating cellular behavior. Here, we analyze the molecular events underlying the primary response to the Dpp/BMP morphogen in Drosophila. Throughout development, Dpp transduction causes the graded transcriptional downregulation of the brinker (brk) gene. We first provide significance for the brk expression gradient by showing that different Brk levels repress distinct combinations of wing genes expressed at different distances from Dpp-secreting cells. We then dissect the brk regulatory region and identify two separable elements with opposite properties, a constitutive enhancer and a Dpp morphogen-regulated silencer. Furthermore, we present genetic and biochemical evidence that the brk silencer serves as a direct target for a protein complex consisting of the Smad homologs Mad/Medea and the zinc finger protein Schnurri. Together, our results provide the molecular framework for a mechanism by which the extracellular Dpp/BMP morphogen establishes a finely tuned, graded read-out of transcriptional repression.

journal_name

Cell

journal_title

Cell

authors

Müller B,Hartmann B,Pyrowolakis G,Affolter M,Basler K

doi

10.1016/s0092-8674(03)00241-1

subject

Has Abstract

pub_date

2003-04-18 00:00:00

pages

221-33

issue

2

eissn

0092-8674

issn

1097-4172

pii

S0092867403002411

journal_volume

113

pub_type

杂志文章

相关文献

CELL文献大全
  • Determination of the amount of homology required for recombination in bacteriophage T4.

    abstract::Homology is an important feature of recombination. We have used the rll cistrons of bacteriophage T4 to determine the extent of homology required for recombination. We varied the amount of homologous DNA available for recombination in both marker rescue experiments and deletion-by-deletion crosses. Our results suggest...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(82)90401-9

    authors: Singer BS,Gold L,Gauss P,Doherty DH

    更新日期:1982-11-01 00:00:00

  • Cell cycle regulated transport controlled by alterations in the nuclear pore complex.

    abstract::Eukaryotic cells have developed mechanisms for regulating the nuclear transport of macromolecules that control various cellular events including movement through defined stages of the cell cycle. In yeast cells, where the nuclear envelope remains intact throughout the cell cycle, these transport regulatory mechanisms ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(03)00986-3

    authors: Makhnevych T,Lusk CP,Anderson AM,Aitchison JD,Wozniak RW

    更新日期:2003-12-26 00:00:00

  • Chromatin fibers are formed by heterogeneous groups of nucleosomes in vivo.

    abstract::Nucleosomes help structure chromosomes by compacting DNA into fibers. To gain insight into how nucleosomes are arranged in vivo, we combined quantitative super-resolution nanoscopy with computer simulations to visualize and count nucleosomes along the chromatin fiber in single nuclei. Nucleosomes assembled in heteroge...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2015.01.054

    authors: Ricci MA,Manzo C,García-Parajo MF,Lakadamyali M,Cosma MP

    更新日期:2015-03-12 00:00:00

  • Hunger states switch a flip-flop memory circuit via a synaptic AMPK-dependent positive feedback loop.

    abstract::Synaptic plasticity in response to changes in physiologic state is coordinated by hormonal signals across multiple neuronal cell types. Here, we combine cell-type-specific electrophysiological, pharmacological, and optogenetic techniques to dissect neural circuits and molecular pathways controlling synaptic plasticity...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2011.07.039

    authors: Yang Y,Atasoy D,Su HH,Sternson SM

    更新日期:2011-09-16 00:00:00

  • Lessons from a failed γ-secretase Alzheimer trial.

    abstract::γ-Secretase proteases have been associated with pathology in Alzheimer disease (AD), but we are just beginning to understand their basic mechanisms and physiological roles. A negative drug trial with a broad spectrum γ-secretase inhibitor in AD patients has severely dampened enthusiasm for the potential of pursuing γ-...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2014.10.016

    authors: De Strooper B

    更新日期:2014-11-06 00:00:00

  • Developmental activation of the H-2K gene is correlated with an increase in DNA methylation.

    abstract::Embryonal carcinoma cell lines present strong developmental analogies with early embryonic cells. Previous studies have shown that treatment of F9 teratocarcinoma cells with retinoic acid induces the expression of the classical transplantation antigens which are indispensable for effective interactions between cells. ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(83)90179-4

    authors: Tanaka K,Appella E,Jay G

    更新日期:1983-12-01 00:00:00

  • Targeted overactivity of beta cell K(ATP) channels induces profound neonatal diabetes.

    abstract::A paradigm for control of insulin secretion is that glucose metabolism elevates cytoplasmic [ATP]/[ADP] in beta cells, closing K(ATP) channels and causing depolarization, Ca2+ entry, and insulin release. Decreased responsiveness of K(ATP) channels to elevated [ATP]/[ADP] should therefore lead to decreased insulin secr...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(00)80701-1

    authors: Koster JC,Marshall BA,Ensor N,Corbett JA,Nichols CG

    更新日期:2000-03-17 00:00:00

  • SnapShot: Functions of Tubulin Posttranslational Modifications.

    abstract::Post-translational modification of tubulin offers a mechanism for functional diversification of microtubules and regulation in a variety of physiological contexts. This SnapShot recaps the current state of understanding of tubulin posttranslational modifications and their functions in the regulation of biological proc...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2018.05.032

    authors: Magiera MM,Singh P,Janke C

    更新日期:2018-05-31 00:00:00

  • Control of transcription through intragenic patterns of nucleosome composition.

    abstract::Several recent papers show that differences in histone modification and the use of histone variants at the 5' and 3' ends of genes influence the location and kinetics of transcriptional initiation. The ultimate target of most epigenetic mechanisms may be the regulation of nucleosome occupancy, which in turn controls a...

    journal_title:Cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.cell.2005.12.010

    authors: Lieb JD,Clarke ND

    更新日期:2005-12-29 00:00:00

  • From ER to Eph receptors: new roles for VAP fragments.

    abstract::Dominantly inherited mutations in an endoplasmic reticulum protein called VAPB have been found in a subset of patients with a rare familial form of amyotrophic lateral sclerosis (ALS). In this issue, Tsuda et al. (2008) identify a secreted form of VAPB that binds directly to Eph receptors inducing their activation and...

    journal_title:Cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.cell.2008.05.028

    authors: Ackerman SL,Cox GA

    更新日期:2008-06-13 00:00:00

  • Analysis of the human endogenous coregulator complexome.

    abstract::Elucidation of endogenous cellular protein-protein interactions and their networks is most desirable for biological studies. Here we report our study of endogenous human coregulator protein complex networks obtained from integrative mass spectrometry-based analysis of 3290 affinity purifications. By preserving weak pr...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2011.05.006

    authors: Malovannaya A,Lanz RB,Jung SY,Bulynko Y,Le NT,Chan DW,Ding C,Shi Y,Yucer N,Krenciute G,Kim BJ,Li C,Chen R,Li W,Wang Y,O'Malley BW,Qin J

    更新日期:2011-05-27 00:00:00

  • A chromatin-dependent role of the fragile X mental retardation protein FMRP in the DNA damage response.

    abstract::Fragile X syndrome, a common form of inherited intellectual disability, is caused by loss of the fragile X mental retardation protein FMRP. FMRP is present predominantly in the cytoplasm, where it regulates translation of proteins that are important for synaptic function. We identify FMRP as a chromatin-binding protei...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2014.03.040

    authors: Alpatov R,Lesch BJ,Nakamoto-Kinoshita M,Blanco A,Chen S,Stützer A,Armache KJ,Simon MD,Xu C,Ali M,Murn J,Prisic S,Kutateladze TG,Vakoc CR,Min J,Kingston RE,Fischle W,Warren ST,Page DC,Shi Y

    更新日期:2014-05-08 00:00:00

  • The canonical Notch signaling pathway: unfolding the activation mechanism.

    abstract::Notch signaling regulates many aspects of metazoan development and tissue renewal. Accordingly, the misregulation or loss of Notch signaling underlies a wide range of human disorders, from developmental syndromes to adult-onset diseases and cancer. Notch signaling is remarkably robust in most tissues even though each ...

    journal_title:Cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.cell.2009.03.045

    authors: Kopan R,Ilagan MX

    更新日期:2009-04-17 00:00:00

  • Torso receptor activity is regulated by a diffusible ligand produced at the extracellular terminal regions of the Drosophila egg.

    abstract::torso encodes a receptor tyrosine kinase (torso) required for anterior and posterior terminal development of the Drosophila embryo. Injecting eggs with in vitro synthesized torso mRNAs revealed that torso activation is governed by an extracellular molecule, presumably the torso ligand, produced at terminal regions of ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(92)90394-r

    authors: Sprenger F,Nüsslein-Volhard C

    更新日期:1992-12-11 00:00:00

  • Congenital immunodeficiency with a regulatory defect in MHC class II gene expression lacks a specific HLA-DR promoter binding protein, RF-X.

    abstract::The expression of MHC class II genes is tightly regulated. One form of congenital severe combined immunodeficiency (SCID) is characterized by a regulatory defect that precludes expression of HLA class II genes. B lymphocyte cell lines from such SCID patients provide a tool for identifying putative regulatory proteins ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(88)90389-3

    authors: Reith W,Satola S,Sanchez CH,Amaldi I,Lisowska-Grospierre B,Griscelli C,Hadam MR,Mach B

    更新日期:1988-06-17 00:00:00

  • Disentangling inborn and acquired immunity in human twins.

    abstract::The human geneticist Archibald Garrod noted in 1931 that, "It is, of necessity, no easy matter to distinguish between immunity which is inborn and that which has been acquired" (The Inborn Factors in Disease). In this issue of Cell, Brodin et al. show that the heritability of blood counts rapidly decreases with age fo...

    journal_title:Cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.cell.2014.12.029

    authors: Casanova JL,Abel L

    更新日期:2015-01-15 00:00:00

  • Nuclear Receptors, RXR, and the Big Bang.

    abstract::Isolation of genes encoding the receptors for steroids, retinoids, vitamin D, and thyroid hormone and their structural and functional analysis revealed an evolutionarily conserved template for nuclear hormone receptors. This discovery sparked identification of numerous genes encoding related proteins, termed orphan re...

    journal_title:Cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.cell.2014.03.012

    authors: Evans RM,Mangelsdorf DJ

    更新日期:2014-03-27 00:00:00

  • Heterozygous familial hypercholesterolemia: failure of normal allele to compensate for mutant allele at a regulated genetic locus.

    abstract::In normal human fibroblasts, the synthesis of a cell surface receptor for plasma low density lipoprotein (LDL) is regulated by a sensitive system of feedback suppression. The number of functional LDL receptors declines by more than 20 fold when cellular stores of esterified cholesterol are increased by incubation of c...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(76)90110-0

    authors: Goldstein JL,Sobhani MK,Faust JR,Brown MS

    更新日期:1976-10-01 00:00:00

  • Seeking new antibiotics in nature's backyard.

    abstract::As the pipeline of new antibiotics slows to a trickle, scientists are developing innovative strategies to unearth antibacterial compounds in unexpected places. ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2006.11.021

    authors: von Bubnoff A

    更新日期:2006-12-01 00:00:00

  • First Approved Kinase Inhibitor for AML.

    abstract::Activating mutations of FLT3 occur in about 30% of acute myeloid leukemia (AML) cases and are associated with relapse and poor prognosis. Midostaurin is the first drug approved for AML since 2000, and the first multi-kinase inhibitor approved for the FLT3-mutant subtype. To view this Bench to Bedside, open or download...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2017.11.007

    authors: Rasko JEJ,Hughes TP

    更新日期:2017-11-16 00:00:00

  • The Striatum Organizes 3D Behavior via Moment-to-Moment Action Selection.

    abstract::Many naturalistic behaviors are built from modular components that are expressed sequentially. Although striatal circuits have been implicated in action selection and implementation, the neural mechanisms that compose behavior in unrestrained animals are not well understood. Here, we record bulk and cellular neural ac...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2018.04.019

    authors: Markowitz JE,Gillis WF,Beron CC,Neufeld SQ,Robertson K,Bhagat ND,Peterson RE,Peterson E,Hyun M,Linderman SW,Sabatini BL,Datta SR

    更新日期:2018-06-28 00:00:00

  • Chromosome missegregation and apoptosis in mice lacking the mitotic checkpoint protein Mad2.

    abstract::The initiation of chromosome segregation at anaphase is linked by the spindle assembly checkpoint to the completion of chromosome-microtubule attachment during metaphase. To determine the function of the mitotic checkpoint protein Mad2 during normal cell division and when mitosis goes awry, we have knocked out Mad2 in...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(00)80875-2

    authors: Dobles M,Liberal V,Scott ML,Benezra R,Sorger PK

    更新日期:2000-06-09 00:00:00

  • Circadian gene expression in individual fibroblasts: cell-autonomous and self-sustained oscillators pass time to daughter cells.

    abstract::The mammalian circadian timing system is composed of a central pacemaker in the suprachiasmatic nucleus (SCN) of the brain and subsidiary oscillators in most peripheral cell types. While oscillators in SCN neurons are known to function in a self-sustained fashion, peripheral oscillators have been thought to damp rapid...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2004.11.015

    authors: Nagoshi E,Saini C,Bauer C,Laroche T,Naef F,Schibler U

    更新日期:2004-11-24 00:00:00

  • Muscle differentiation in normal and cleavage-arrested mutant embryos of Caenorhabditis elegans.

    abstract::The differentiation of body-wall muscle cells was studied in the nematode Caenorhabditis elegans. Specific antibodies to myosin and paramyosin, major protein constituents of differentiated muscle, react with mesodermal cells in wild-type embryos towards the end of the first half of embryogenesis. Immunoreactive cells ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(82)90025-3

    authors: Gossett LA,Hecht RM,Epstein HF

    更新日期:1982-08-01 00:00:00

  • Mapping Polycomb-repressed domains in the bithorax complex using in vivo formaldehyde cross-linked chromatin.

    abstract::The Polycomb group (Pc-G) proteins are responsible for keeping developmental regulators, like homeotic genes, stably and inheritably repressed during Drosophila development. Several similarities to a protein class involved in heterochromatin formation suggest that the Pc-G exerts its function at the higher order chrom...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(93)90328-n

    authors: Orlando V,Paro R

    更新日期:1993-12-17 00:00:00

  • A novel all helix fold of the AP180 amino-terminal domain for phosphoinositide binding and clathrin assembly in synaptic vesicle endocytosis.

    abstract::Clathrin-mediated endocytosis plays a major role in retrieving synaptic vesicles from the plasma membrane following exocytosis. This endocytic process requires AP180 (or a homolog), which promotes the assembly and restricts the size of clathrin-coated vesicles. The highly conserved 33 kDa amino-terminal domain of AP18...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(01)00230-6

    authors: Mao Y,Chen J,Maynard JA,Zhang B,Quiocho FA

    更新日期:2001-02-09 00:00:00

  • Linking RNA polymerase backtracking to genome instability in E. coli.

    abstract::Frequent codirectional collisions between the replisome and RNA polymerase (RNAP) are inevitable because the rate of replication is much faster than that of transcription. Here we show that, in E. coli, the outcome of such collisions depends on the productive state of transcription elongation complexes (ECs). Codirect...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2011.07.034

    authors: Dutta D,Shatalin K,Epshtein V,Gottesman ME,Nudler E

    更新日期:2011-08-19 00:00:00

  • An Unbiased Screen for Human Cytomegalovirus Identifies Neuropilin-2 as a Central Viral Receptor.

    abstract::Characterizing cell surface receptors mediating viral infection is critical for understanding viral tropism and developing antiviral therapies. Nevertheless, due to challenges associated with detecting protein interactions on the cell surface, the host receptors of many human pathogens remain unknown. Here, we build a...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2018.06.028

    authors: Martinez-Martin N,Marcandalli J,Huang CS,Arthur CP,Perotti M,Foglierini M,Ho H,Dosey AM,Shriver S,Payandeh J,Leitner A,Lanzavecchia A,Perez L,Ciferri C

    更新日期:2018-08-23 00:00:00

  • Cell death: a new Par-4 the TRAIL.

    abstract::The protein Par-4 acts in the cytoplasm to trigger cell death signaling via caspase activation and the mitochondrial release of cytochrome c. Burikhanov et al. (2009) now provide surprising evidence that Par-4 can also promote apoptosis from outside the cell, after its secretion in response to endoplasmic reticulum st...

    journal_title:Cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.cell.2009.07.007

    authors: Hart LS,El-Deiry WS

    更新日期:2009-07-23 00:00:00

  • Use of a lacZ fusion to study the role of the spoO genes of Bacillus subtilis in developmental regulation.

    abstract::A mutation in any one of eight spoO genes of Bacillus subtilis blocks the process of spore formation at its earliest stage. To investigate how the products of the spoO genes may be involved in developmental gene expression, we fused the lacZ gene of E. coli to spoVG, a sporulation gene whose induction at the onset of ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(83)90230-1

    authors: Zuber P,Losick R

    更新日期:1983-11-01 00:00:00