scholarly journals Boundary Dpp promotes growth of medial and lateral regions of the Drosophila wing

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Lara Barrio ◽  
Marco Milán
Keyword(s):  
Temperature Sensitive ◽  
Drosophila Wing ◽  
Compartment Boundary ◽  
Absolute Requirement ◽  
Proliferative Growth ◽  
Graded Activity ◽  
Tissue Size ◽  
Wing Growth ◽  
Intense Debate

The gradient of Decapentaplegic (Dpp) in the Drosophila wing has served as a paradigm to characterize the role of morphogens in regulating patterning. However, the role of this gradient in regulating tissue size is a topic of intense debate as proliferative growth is homogenous. Here, we combined the Gal4/UAS system and a temperature-sensitive Gal80 molecule to induce RNAi-mediated depletion of dpp and characterise the spatial and temporal requirement of Dpp in promoting growth. We show that Dpp emanating from the AP compartment boundary is required throughout development to promote growth by regulating cell proliferation and tissue size. Dpp regulates growth and proliferation rates equally in central and lateral regions of the developing wing appendage and reduced levels of Dpp affects similarly the width and length of the resulting wing. We also present evidence supporting the proposal that graded activity of Dpp is not an absolute requirement for wing growth.

pVHL-mediated SMAD3 degradation suppresses TGF-β signaling

2021 ◽  
Vol 221 (1) ◽  
Author(s):  
Jun Zhou ◽  
Yasamin Dabiri ◽  
Rodrigo A. Gama-Brambila ◽  
Shahrouz Ghafoory ◽  
Mukaddes Altinbay ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Tissue Homeostasis ◽  
Wing Development ◽  
Dynamic Regulation ◽  
Drosophila Wing ◽  
Wing Growth ◽  
Expression And Activity

Transforming growth factor β (TGF-β) signaling plays a fundamental role in metazoan development and tissue homeostasis. However, the molecular mechanisms concerning the ubiquitin-related dynamic regulation of TGF-β signaling are not thoroughly understood. Using a combination of proteomics and an siRNA screen, we identify pVHL as an E3 ligase for SMAD3 ubiquitination. We show that pVHL directly interacts with conserved lysine and proline residues in the MH2 domain of SMAD3, triggering degradation. As a result, the level of pVHL expression negatively correlates with the expression and activity of SMAD3 in cells, Drosophila wing, and patient tissues. In Drosophila, loss of pVHL leads to the up-regulation of TGF-β targets visible in a downward wing blade phenotype, which is rescued by inhibition of SMAD activity. Drosophila pVHL expression exhibited ectopic veinlets and reduced wing growth in a similar manner as upon loss of TGF-β/SMAD signaling. Thus, our study demonstrates a conserved role of pVHL in the regulation of TGF-β/SMAD3 signaling in human cells and Drosophila wing development.

Role of knot (kn) in Wing Patterning in Drosophila

Genetics ◽  
1997 ◽  
Vol 147 (3) ◽  
pp. 1203-1212 ◽  
Author(s):  
Katerina Nestoras ◽  
Helena Lee ◽  
Jym Mohler
Keyword(s):  
Hedgehog Signaling ◽  
Imaginal Disc ◽  
Hedgehog Signaling Pathway ◽  
Posterior Compartment ◽  
Drosophila Wing ◽  
Compartment Boundary ◽  
Hh Signaling ◽  
Embryonic Segmentation ◽  
Anterior Posterior

We have undertaken a genetic analysis of new strong alleles of knot (kn). The original kn1 mutation causes an alteration of wing patterning similar to that associated with mutations of fused (fu), an apparent fusion of veins 3 and 4 in the wing. However, unlike fu, strong kn mutations do not affect embryonic segmentation and indicate that kn is not a component of a general Hh (Hedgehog)-signaling pathway. Instead we find that kn has a specific role in those cells of the wing imaginal disc that are subject to ptc-mediated Hh-signaling. Our results suggest a model for patterning the medial portion of the Drosophila wing, whereby the separation of veins 3 and 4 is maintained by kn activation in the intervening region in response to Hh-signaling across the adjacent anterior-posterior compartment boundary.

wingless expression mediates determination of peripheral nervous system elements in late stages of Drosophila wing disc development

Development ◽  
1993 ◽  
Vol 118 (2) ◽  
pp. 427-438 ◽  
Author(s):  
R.G. Phillips ◽  
J.R. Whittle
Keyword(s):  
Imaginal Disc ◽  
Time Course ◽  
Wing Disc ◽  
Temperature Sensitive ◽  
Spatial Patterning ◽  
Proneural Gene ◽  
Drosophila Wing ◽  
Late Stages

We have used conditional wingless genotypes to dissect the role of this gene in late stages of wing disc development. One of these genotypes (wgIL/wg-lacZ) is simultaneously a reporter of wingless transcription and temperature-sensitive for wingless function, and has allowed us to define its pattern of transcription in the absence of wingless activity. The primordia of a subset of the bristles of the notum, which develop in or immediately adjacent to wingless-expressing cells, depend upon wingless activity. The time-course of this contribution and the effect on proneural gene expression together suggest that wingless may regulate the activity of products of the achaete-scute complex in proneural clusters. wingless activity is also required at the presumptive wing margin and is a necessary precondition for the change in proliferation pattern in this region. The involvement of wingless in transducing or mediating positional signals for spatial patterning in imaginal disc development is discussed.

scholarly journals Free will and neurosurgical resections of the supplementary motor area: a critical review

2021 ◽  
Vol 163 (5) ◽  
pp. 1229-1237 ◽  
Author(s):  
Rickard L Sjöberg
Keyword(s):  
Executive Function ◽  
Free Will ◽  
Corticospinal Tract ◽  
Supplementary Motor Area ◽  
Personal Responsibility ◽  
Motor Area ◽  
Simple Motor ◽  
Motor Actions ◽  
Intense Debate

Abstract Background Research suggests that unconscious activity in the supplementary motor area (SMA) precedes not only certain simple motor actions but also the point at which we become aware of our intention to perform such actions. The extent to which these findings have implications for our understanding of the concepts of free will and personal responsibility has been subject of intense debate during the latest four decades. Methods This research is discussed in relation to effects of neurosurgical removal of the SMA in a narrative review. Results Removal of the SMA typically causes a transient inability to perform non-stimulus-driven, voluntary actions. This condition, known as the SMA syndrome, does not appear to be associated with a loss of sense of volition but with a profound disruption of executive function/cognitive control. Conclusions The role of the SMA may be to serve as a gateway between the corticospinal tract and systems for executive function. Such systems are typically seen as tools for conscious decisions. What is known about effects of SMA resections would thus seem to suggest a view that is compatible with concepts of personal responsibility. However, the philosophical question whether free will exists cannot be definitely resolved on the basis of these observations.

scholarly journals Role of SpoVA Proteins in Release of Dipicolinic Acid during Germination of Bacillus subtilis Spores Triggered by Dodecylamine or Lysozyme

2006 ◽  
Vol 189 (5) ◽  
pp. 1565-1572 ◽  
Author(s):  
Venkata Ramana Vepachedu ◽  
Peter Setlow
Keyword(s):  
Bacillus Subtilis ◽  
Small Molecules ◽  
Spore Germination ◽  
Dipicolinic Acid ◽  
Temperature Sensitive ◽  
Wild Type ◽  
Ph Optimum ◽  
Inner Membrane ◽  
Temperature Sensitive Mutants

ABSTRACT The release of dipicolinic acid (DPA) during the germination of Bacillus subtilis spores by the cationic surfactant dodecylamine exhibited a pH optimum of ∼9 and a temperature optimum of 60°C. DPA release during dodecylamine germination of B. subtilis spores with fourfold-elevated levels of the SpoVA proteins that have been suggested to be involved in the release of DPA during nutrient germination was about fourfold faster than DPA release during dodecylamine germination of wild-type spores and was inhibited by HgCl2. Spores carrying temperature-sensitive mutants in the spoVA operon were also temperature sensitive in DPA release during dodecylamine germination as well as in lysozyme germination of decoated spores. In addition to DPA, dodecylamine triggered the release of amounts of Ca2+ almost equivalent to those of DPA, and at least one other abundant spore small molecule, glutamic acid, was released in parallel with Ca2+ and DPA. These data indicate that (i) dodecylamine triggers spore germination by opening a channel in the inner membrane for Ca2+-DPA and other small molecules, (ii) this channel is composed at least in part of proteins, and (iii) SpoVA proteins are involved in the release of Ca2+-DPA and other small molecules during spore germination, perhaps by being a part of a channel in the spore's inner membrane.

scholarly journals Labor Standards: Where Do They Belong on the International Trade Agenda?

2001 ◽  
Vol 15 (3) ◽  
pp. 89-112 ◽  
Author(s):  
Drusilla K Brown
Keyword(s):  
Developing Countries ◽  
International Trade ◽  
Labor Standards ◽  
Labor Regulation ◽  
National Sovereignty ◽  
The Past ◽  
Trade Sanctions ◽  
Technical Advice ◽  
Intense Debate

During the past decade, universal labor standards have become the focus of intense debate. Advocates argue from humanitarian concerns and the interests of industrialized-country labor, seeking enforcement with WTO sanctions. Opponents regard labor regulation as a matter of national sovereignty, challenge the effectiveness of trade sanctions, and prefer the ILO emphasis on dialogue, monitoring and technical advice. This paper analyzes the labor standards debate, with specific attention to the analytical underpinnings of universal rules; evidence linking weak labor protections in developing countries to industrialized country wages; and the role of labor standards in WTO negotiations.

scholarly journals A High Copy Suppressor Screen Reveals Genetic Interactions Between BET3 and a New Gene: Evidence for a Novel Complex in ER-to-Golgi Transport

Genetics ◽  
1998 ◽  
Vol 149 (2) ◽  
pp. 833-841
Author(s):  
Yu Jiang ◽  
Al Scarpa ◽  
Li Zhang ◽  
Shelly Stone ◽  
Ed Feliciano ◽  
...  
Keyword(s):  
Growth Defect ◽  
Carboxypeptidase Y ◽  
Temperature Sensitive ◽  
Yeast Saccharomyces Cerevisiae ◽  
Specific Suppression ◽  
Golgi Transport ◽  
New Gene ◽  
Insight Into ◽  
Suppressor Screen

Abstract The BET3 gene in the yeast Saccharomyces cerevisiae encodes a 22-kD hydrophilic protein that is required for vesicular transport between the ER and Golgi complex. To gain insight into the role of Bet3p, we screened for genes that suppress the growth defect of the temperature-sensitive bet3 mutant at 34°. This high copy suppressor screen resulted in the isolation of a new gene, called BET5. BET5 encodes an essential 18-kD hydrophilic protein that in high copy allows growth of the bet3-1 mutant, but not other ER accumulating mutants. This strong and specific suppression is consistent with the fact that Bet3p and Bet5p are members of the same complex. Using PCR mutagenesis, we generated a temperature-sensitive mutation in BET5 (bet5-1) that blocks the transport of carboxypeptidase Y to the vacuole and prevents secretion of the yeast pheromone α-factor at 37°. The precursor forms of these proteins that accumulate in this mutant are indicative of a block in membrane traffic between the ER and Golgi apparatus. High copy suppressors of the bet5-1 mutant include several genes whose products are required for ER-to-Golgi transport (BET1, SEC22, USO1 and DSS4) and the maintenance of the Golgi (ANP1). These findings support the hypothesis that Bet5p acts in conjunction with Bet3p to mediate a late stage in ER-to-Golgi transport. The identification of mammalian homologues of Bet3p and Bet5p implies that the Bet3p/Bet5p complex is highly conserved in evolution.

Synaptojanin family members are implicated in endocytic membrane traffic in yeast

1998 ◽  
Vol 111 (22) ◽  
pp. 3347-3356 ◽  
Author(s):  
B. Singer-Kruger ◽  
Y. Nemoto ◽  
L. Daniell ◽  
S. Ferro-Novick ◽  
P. De Camilli
Keyword(s):  
Synaptic Vesicles ◽  
Direct Evidence ◽  
Family Members ◽  
Fluid Phase ◽  
Growth Defect ◽  
Temperature Sensitive ◽  
Close Link ◽  
Fluid Phase Endocytosis ◽  
Synaptojanin 1

The synaptojanins represent a subfamily of inositol 5′-phosphatases that contain an NH2-terminal Sac1p homology domain. A nerve terminal-enriched synaptojanin, synaptojanin 1, was previously proposed to participate in the endocytosis of synaptic vesicles and actin function. The genome of Saccharomyces cerevisiae contains three synaptojanin-like genes (SJL1, SJL2 and SJL3), none of which is essential for growth. We report here that a yeast mutant lacking SJL1 and SJL2 (Deltasjl1 Deltasjl2) exhibits a severe defect in receptor-mediated and fluid-phase endocytosis. A less severe endocytic defect is present in a Deltasjl2 Deltasjl3 mutant, while endocytosis is normal in a Deltasjl1 Deltasjl3 mutant. None of the mutants are impaired in invertase secretion. The severity of the endocytic impairment of the sjl double mutants correlates with the severity of actin and polarity defects. Furthermore, the deletion of SJL1 suppresses the temperature-sensitive growth defect of sac6, a mutant in yeast fimbrin, supporting a role for synaptojanin family members in actin function. These findings provide a first direct evidence for a role of synaptojanin family members in endocytosis and provide further evidence for a close link between endocytosis and actin function.

Altered Regulation of Potassium and Calcium Channels by GABAB and Adenosine Receptors in Hippocampal Neurons From Mice Lacking Gαo

2000 ◽  
Vol 83 (2) ◽  
pp. 1010-1018 ◽  
Author(s):  
Gabriela J. Greif ◽  
Deborah L. Sodickson ◽  
Bruce P. Bean ◽  
Eva J. Neer ◽  
Ulrike Mende
Keyword(s):  
Time Constant ◽  
Hippocampal Neurons ◽  
Ionic Currents ◽  
Absolute Requirement ◽  
Voltage Dependent ◽  
Hippocampal Ca3 ◽  
Ca3 Neurons ◽  
Inwardly Rectifying ◽  
G Protein Coupled

To examine the role of Go in modulation of ion channels by neurotransmitter receptors, we characterized modulation of ionic currents in hippocampal CA3 neurons from mice lacking both isoforms of Gαo. In CA3 neurons from Gαo −/− mice, 2-chloro-adenosine and the GABAB-receptor agonist baclofen activated inwardly rectifying K+ currents and inhibited voltage-dependent Ca2+ currents just as effectively as in Gαo +/+ littermates. However, the kinetics of transmitter action were dramatically altered in Gαo −/− mice in that recovery on washout of agonist was much slower. For example, recovery from 2-chloro-adenosine inhibition of calcium current was more than fourfold slower in neurons from Gαo −/− mice [time constant of 12.0 ± 0.8 (SE) s] than in neurons from Gαo +/+ mice (time constant of 2.6 ± 0.2 s). Recovery from baclofen effects was affected similarly. In neurons from control mice, effects of both baclofen and 2-chloro-adenosine on Ca2+ currents and K+currents were abolished by brief exposure to external N-ethyl-maleimide (NEM). In neurons lacking Gαo, some inhibition of Ca2+ currents by baclofen remained after NEM treatment, whereas baclofen activation of K+ currents and both effects of 2-chloro-adenosine were abolished. These results show that modulation of Ca2+ and K+ currents by G protein-coupled receptors in hippocampal neurons does not have an absolute requirement for Gαo. However, modulation is changed in the absence of Gαo in having much slower recovery kinetics. A likely possibility is that the very abundant Gαo is normally used but, when absent, can readily be replaced by G proteins with different properties.

scholarly journals Phosphoregulation of the intracellular termini of K+-Cl− cotransporter 2 (KCC2) enables flexible control of its activity

2018 ◽  
Vol 293 (44) ◽  
pp. 16984-16993 ◽  
Author(s):  
Antje Cordshagen ◽  
Wiebke Busch ◽  
Michael Winklhofer ◽  
Hans Gerd Nothwang ◽  
Anna-Maria Hartmann
Keyword(s):  
Intrinsic Activity ◽  
Hek 293 ◽  
Flexible Control ◽  
Mediated Effects ◽  
293 Cells ◽  
Bona Fide ◽  
Graded Activity ◽  
First Time ◽  
Increased Activity

The pivotal role of K+-Cl− cotransporter 2 (KCC2) in inhibitory neurotransmission and severe human diseases fosters interest in understanding posttranslational regulatory mechanisms such as (de)phosphorylation. Here, the regulatory role of the five bona fide phosphosites Ser31, Thr34, Ser932, Thr999, and Thr1008 was investigated by the use of alanine and aspartate mutants. Tl+-based flux analyses in HEK-293 cells demonstrated increased transport activity for S932D (mimicking phosphorylation) and T1008A (mimicking dephosphorylation), albeit to a different extent. Increased activity was due to changes in intrinsic activity, as it was not caused by increased cell-surface abundance. Substitutions of Ser31, Thr34, or Thr999 had no effect. Additionally, we show that the indirect actions of the known KCC2 activators staurosporine and N-ethylmaleimide (NEM) involved multiple phosphosites. S31D, T34A, S932A/D, T999A, or T1008A/D abrogated staurosporine mediated stimulation, and S31A, T34D, or S932D abolished NEM-mediated stimulation. This demonstrates for the first time differential effects of staurosporine and NEM on KCC2. In addition, the staurosporine-mediated effects involved both KCC2 phosphorylation and dephosphorylation with Ser932 and Thr1008 being bona fide target sites. In summary, our data reveal a complex phosphoregulation of KCC2 that provides the transporter with a toolbox for graded activity and integration of different signaling pathways.

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