Faculty Opinions recommendation of Recruitment of Jub by α-catenin promotes Yki activity and Drosophila wing growth.

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.

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

eLife ◽

10.7554/elife.22013 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 14

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.

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Synergistic signaling by two BMP ligands through the SAX and TKV receptors controls wing growth and patterning in Drosophila

Development ◽

10.1242/dev.125.20.3977 ◽

1998 ◽

Vol 125 (20) ◽

pp. 3977-3987 ◽

Cited By ~ 14

Author(s):

T.E. Haerry ◽

O. Khalsa ◽

M.B. O'Connor ◽

K.A. Wharton

Keyword(s):

Transcriptional Response ◽

Type I ◽

Drosophila Wing ◽

Receptor Concentration ◽

Wing Discs ◽

Response Thresholds ◽

Multiple Ligands ◽

Wing Growth ◽

Concentration Levels ◽

Signaling Activity

In Drosophila wing discs, a morphogen gradient of DPP has been proposed to determine the transcriptional response thresholds of the downstream genes sal and omb. We present evidence that the concentration of the type I receptor TKV must be low to allow long-range DPP diffusion. Low TKV receptor concentrations result, however, in low signaling activity. To enhance signaling at low DPP concentrations, we find that a second ligand, GBB, augments DPP/TKV activity. GBB signals primarily through the type I receptor SAX, which synergistically enhances TKV signaling and is required for proper OMB expression. We show that OMB expression in wing discs requires synergistic signaling by multiple ligands and receptors to overcome the limitations imposed on DPP morphogen function by receptor concentration levels.

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Genetic characterization of ebi reveals its critical role in Drosophila wing growth

Fly ◽

10.4161/fly.5.4.18276 ◽

2011 ◽

Vol 5 (4) ◽

pp. 291-303 ◽

Cited By ~ 3

Author(s):

Steven J. Marygold ◽

Cherryl Walker ◽

Mariam Orme ◽

Sally Leevers

Keyword(s):

Genetic Characterization ◽

Critical Role ◽

Drosophila Wing ◽

Wing Growth

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Control of Drosophila wing size by morphogen range and hormonal gating

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2018196117 ◽

2020 ◽

Vol 117 (50) ◽

pp. 31935-31944 ◽

Cited By ~ 1

Author(s):

Joseph Parker ◽

Gary Struhl

Keyword(s):

Cellular Response ◽

Steroid Hormone ◽

Experimental Paradigm ◽

Wing Size ◽

Larval Life ◽

Drosophila Wing ◽

The Right ◽

Wing Growth ◽

Gain Body Mass ◽

Correct Size

The stereotyped dimensions of animal bodies and their component parts result from tight constraints on growth. Yet, the mechanisms that stop growth when organs reach the right size are unknown. Growth of the Drosophila wing—a classic paradigm—is governed by two morphogens, Decapentaplegic (Dpp, a BMP) and Wingless (Wg, a Wnt). Wing growth during larval life ceases when the primordium attains full size, concomitant with the larval-to-pupal molt orchestrated by the steroid hormone ecdysone. Here, we block the molt by genetically dampening ecdysone production, creating an experimental paradigm in which the wing stops growing at the correct size while the larva continues to feed and gain body mass. Under these conditions, we show that wing growth is limited by the ranges of Dpp and Wg, and by ecdysone, which regulates the cellular response to their signaling activities. Further, we present evidence that growth terminates because of the loss of two distinct modes of morphogen action: 1) maintenance of growth within the wing proper and 2) induced growth of surrounding “pre-wing” cells and their recruitment into the wing. Our results provide a precedent for the control of organ size by morphogen range and the hormonal gating of morphogen action.

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Control of Drosophila wing growth by the vestigial quadrant enhancer

Development ◽

10.1242/dev.006445 ◽

2007 ◽

Vol 134 (16) ◽

pp. 3011-3020 ◽

Cited By ~ 38

Author(s):

M. Zecca ◽

G. Struhl

Keyword(s):

Drosophila Wing ◽

Wing Growth

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A Feed-Forward Circuit Linking Wingless, Fat-Dachsous Signaling, and the Warts-Hippo Pathway to Drosophila Wing Growth

PLoS Biology ◽

10.1371/journal.pbio.1000386 ◽

2010 ◽

Vol 8 (6) ◽

pp. e1000386 ◽

Cited By ~ 92

Author(s):

Myriam Zecca ◽

Gary Struhl

Keyword(s):

Hippo Pathway ◽

Feed Forward ◽

Drosophila Wing ◽

Wing Growth

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Asymmetric requirement of Dpp/BMP morphogen dispersal in the Drosophila wing disc

10.1101/2020.11.23.394379 ◽

2020 ◽

Author(s):

Shinya Matsuda ◽

Jonas V. Schaefer ◽

Yusuke Mii ◽

Yutaro Hori ◽

Dimitri Bieli ◽

...

Keyword(s):

Positional Information ◽

Wing Disc ◽

Morphogen Gradients ◽

Drosophila Wing ◽

Control Growth ◽

Protein Functions ◽

Underlying Mechanisms ◽

Anterior Patterning ◽

Wing Growth ◽

And Control

SummaryMorphogen gradients provide positional information and control growth in developing tissues, but the underlying mechanisms remain largely unknown due to lack of tools manipulating morphogen gradients. Here, we generate two synthetic protein binder tools manipulating different parameters of Decapentaplegic (Dpp), a morphogen thought to control Drosophila wing disc patterning and growth by dispersal; while HA trap blocks Dpp dispersal, Dpp trap blocks Dpp dispersal and signaling in the source cells. Using these tools, we found that while posterior patterning and growth require Dpp dispersal, anterior patterning and growth largely proceed without Dpp dispersal. We show that dpp transcriptional refinement from an initially uniform to a localized expression and persistent signaling in transient dpp source cells render the anterior compartment robust to blocking Dpp dispersal. Furthermore, neither Dpp dispersal nor signaling is critical for lateral wing growth. These results challenge Dpp dispersal-centric mechanisms, and demonstrate the utility of customized protein binder tools to dissect protein functions.

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Dpp controls growth and patterning in Drosophila wing precursors through distinct modes of action

eLife ◽

10.7554/elife.22546 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 30

Author(s):

Pablo Sanchez Bosch ◽

Ruta Ziukaite ◽

Cyrille Alexandre ◽

Konrad Basler ◽

Jean-Paul Vincent

Keyword(s):

Target Genes ◽

Positional Information ◽

Cell Fates ◽

Drosophila Wing ◽

The Subject ◽

Spatio Temporal ◽

Wing Growth ◽

The Relationship ◽

Anterior Posterior ◽

Growth Threshold

Dpp, a member of the BMP family, is a morphogen that specifies positional information in Drosophila wing precursors. In this tissue, Dpp expressed along the anterior-posterior boundary forms a concentration gradient that controls the expression domains of target genes, which in turn specify the position of wing veins. Dpp also promotes growth in this tissue. The relationship between the spatio-temporal profile of Dpp signalling and growth has been the subject of debate, which has intensified recently with the suggestion that the stripe of Dpp is dispensable for growth. With two independent conditional alleles of dpp, we find that the stripe of Dpp is essential for wing growth. We then show that this requirement, but not patterning, can be fulfilled by uniform, low level, Dpp expression. Thus, the stripe of Dpp ensures that signalling remains above a pro-growth threshold, while at the same time generating a gradient that patterns cell fates.

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