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

Development ◽  
1998 ◽  
Vol 125 (20) ◽  
pp. 3977-3987 ◽  
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.

Quantitative EM of gap junction distribution in mutant drosophila wing discs

1983 ◽  
Vol 41 ◽  
pp. 720-721
Author(s):  
J.S. Ryerse
Keyword(s):  
Gap Junctions ◽  
Growth Control ◽  
Intercellular Junctions ◽  
Wing Disc ◽  
En Bloc ◽  
Metabolic Cooperation ◽  
Drosophila Wing ◽  
Adult Wing ◽  
Wing Discs ◽  
Wing Pouch

Gap junctions are intercellular junctions found in both vertebrates and invertebrates through which ions and small molecules can pass. Their distribution in tissues could be of critical importance for ionic coupling or metabolic cooperation between cells or for regulating the intracellular movement of growth control and pattern formation factors. Studies of the distribution of gap junctions in mutants which develop abnormally may shed light upon their role in normal development. I report here the distribution of gap junctions in the wing pouch of 3 Drosophila wing disc mutants, vg (vestigial) a cell death mutant, 1(2)gd (lethal giant disc) a pattern abnormality mutant and 1(2)gl (lethal giant larva) a neoplastic mutant and compare these with wildtype wing discs.The wing pouch (the anlagen of the adult wing blade) of a wild-type wing disc is shown in Fig. 1 and consists of columnar cells (Fig. 5) joined by gap junctions (Fig. 6). 14000x EMs of conventionally processed, UA en bloc stained, longitudinally sectioned wing pouches were enlarged to 45000x with a projector and tracings were made on which the lateral plasma membrane (LPM) and gap junctions were marked.

scholarly journals Recruitment of Jub by α-catenin promotes Yki activity and Drosophila wing growth

2019 ◽  
Vol 132 (5) ◽  
pp. jcs222018 ◽  
Author(s):  
Herve Alégot ◽  
Christopher Markosian ◽  
Cordelia Rauskolb ◽  
Janice Yang ◽  
Elmira Kirichenko ◽  
...  
Keyword(s):  
Drosophila Wing ◽  
Wing Growth

scholarly journals Endocytosis of Wingless via a dynamin-independent pathway is necessary for signaling in Drosophila wing discs

2016 ◽  
Vol 113 (45) ◽  
pp. E6993-E7002 ◽  
Author(s):  
Anupama Hemalatha ◽  
Chaitra Prabhakara ◽  
Satyajit Mayor
Keyword(s):  
Signal Transduction ◽  
Wing Disc ◽  
Low Ph ◽  
Endocytic Pathway ◽  
Apical Surface ◽  
Receptor Complexes ◽  
Drosophila Wing ◽  
Wing Discs ◽  
Ph Dependent ◽  
Endocytic Pathways

Endocytosis of ligand-receptor complexes regulates signal transduction during development. In particular, clathrin and dynamin-dependent endocytosis has been well studied in the context of patterning of the Drosophila wing disc, wherein apically secreted Wingless (Wg) encounters its receptor, DFrizzled2 (DFz2), resulting in a distinctive dorso-ventral pattern of signaling outputs. Here, we directly track the endocytosis of Wg and DFz2 in the wing disc and demonstrate that Wg is endocytosed from the apical surface devoid of DFz2 via a dynamin-independent CLIC/GEEC pathway, regulated by Arf1, Garz, and class I PI3K. Subsequently, Wg containing CLIC/GEEC endosomes fuse with DFz2-containing vesicles derived from the clathrin and dynamin-dependent endocytic pathway, which results in a low pH-dependent transfer of Wg to DFz2 within the merged and acidified endosome to initiate Wg signaling. The employment of two distinct endocytic pathways exemplifies a mechanism wherein cells in tissues leverage multiple endocytic pathways to spatially regulate signaling.

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.

scholarly journals Divergent functions and distinct localization of the Notch ligands DLL1 and DLL3 in vivo

2007 ◽  
Vol 178 (3) ◽  
pp. 465-476 ◽  
Author(s):  
Insa Geffers ◽  
Katrin Serth ◽  
Gavin Chapman ◽  
Robert Jaekel ◽  
Karin Schuster-Gossler ◽  
...  
Keyword(s):  
Golgi Apparatus ◽  
Mouse Embryos ◽  
Functional Equivalence ◽  
Presomitic Mesoderm ◽  
Drosophila Wing ◽  
Wing Discs ◽  
Golgi Network ◽  
Notch Ligands

The Notch ligands Dll1 and Dll3 are coexpressed in the presomitic mesoderm of mouse embryos. Despite their coexpression, mutations in Dll1 and Dll3 cause strikingly different defects. To determine if there is any functional equivalence, we replaced Dll1 with Dll3 in mice. Dll3 does not compensate for Dll1; DLL1 activates Notch in Drosophila wing discs, but DLL3 does not. We do not observe evidence for antagonism between DLL1 and DLL3, or repression of Notch activity in mice or Drosophila. In vitro analyses show that differences in various domains of DLL1 and DLL3 individually contribute to their biochemical nonequivalence. In contrast to endogenous DLL1 located on the surface of presomitic mesoderm cells, we find endogenous DLL3 predominantly in the Golgi apparatus. Our data demonstrate distinct in vivo functions for DLL1 and DLL3. They suggest that DLL3 does not antagonize DLL1 in the presomitic mesoderm and warrant further analyses of potential physiological functions of DLL3 in the Golgi network.

scholarly journals The Potential Role of the ZIKV NS5 Nuclear Spherical-Shell Structures in Cell Type-Specific Host Immune Modulation during ZIKV Infection

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1519 ◽  
Author(s):  
Min Jie Alvin Tan ◽  
Kitti Wing Ki Chan ◽  
Ivan H. W. Ng ◽  
Sean Yao Zu Kong ◽  
Chin Piaw Gwee ◽  
...  
Keyword(s):  
Spherical Shell ◽  
Immune Modulation ◽  
Transcriptional Response ◽  
Type I ◽  
Primary Role ◽  
Structural Protein ◽  
Cell Type ◽  
Zikv Infection ◽  
Cell Type Specific

The Zika virus (ZIKV) non-structural protein 5 (NS5) plays multiple viral and cellular roles during infection, with its primary role in virus RNA replication taking place in the cytoplasm. However, immunofluorescence assay studies have detected the presence of ZIKV NS5 in unique spherical shell-like structures in the nuclei of infected cells, suggesting potentially important cellular roles of ZIKV NS5 in the nucleus. Hence ZIKV NS5′s subcellular distribution and localization must be tightly regulated during ZIKV infection. Both ZIKV NS5 expression or ZIKV infection antagonizes type I interferon signaling, and induces a pro-inflammatory transcriptional response in a cell type-specific manner, but the mechanisms involved and the role of nuclear ZIKV NS5 in these cellular functions has not been elucidated. Intriguingly, these cells originate from the brain and placenta, which are also organs that exhibit a pro-inflammatory signature and are known sites of pathogenesis during ZIKV infection in animal models and humans. Here, we discuss the regulation of the subcellular localization of the ZIKV NS5 protein, and its putative role in the induction of an inflammatory response and the occurrence of pathology in specific organs during ZIKV infection.

scholarly journals Human type II receptor for bone morphogenic proteins (BMPs): extension of the two-kinase receptor model to the BMPs.

1995 ◽  
Vol 15 (7) ◽  
pp. 3479-3486 ◽  
Author(s):  
F Liu ◽  
F Ventura ◽  
J Doody ◽  
J Massagué
Keyword(s):  
Transforming Growth Factor Beta ◽  
Mammalian Cells ◽  
Transforming Growth Factor ◽  
Transcriptional Response ◽  
Family Type ◽  
Type I ◽  
Type Ii ◽  
Receptor System ◽  
Bone Morphogenic Proteins ◽  
Bmp Receptors

Bone morphogenic proteins (BMPs) are universal regulators of animal development. We report the identification and cloning of the BMP type II receptor (BMPR-II), a missing component of this receptor system in vertebrates. BMPR-II is a transmembrane serine/threonine kinase that binds BMP-2 and BMP-7 in association with multiple type I receptors, including BMPR-IA/Brk1, BMPR-IB, and ActR-I, which is also an activin type I receptor. Cloning of BMPR-II resulted from a strong interaction of its cytoplasmic domain with diverse transforming growth factor beta family type I receptor cytoplasmic domains in a yeast two-hybrid system. In mammalian cells, however, the interaction of BMPR-II is restricted to BMP type I receptors and is ligand dependent. BMPR-II binds BMP-2 and -7 on its own, but binding is enhanced by coexpression of type I BMP receptors. BMP-2 and BMP-7 can induce a transcriptional response when added to cells coexpressing ActR-I and BMPR-II but not to cells expressing either receptor alone. The kinase activity of both receptors is essential for signaling. Thus, despite their ability to bind to type I and II receptors receptors separately, BMPs appear to require the cooperation of these two receptors for optimal binding and for signal transduction. The combinatorial nature of these receptors and their capacity to crosstalk with the activin receptor system may underlie the multifunctional nature of their ligands.

Smad7 selectively interferes with different pathways of activin signaling and inhibits erythroid leukemia cell differentiation

Blood ◽  
2000 ◽  
Vol 95 (11) ◽  
pp. 3371-3379 ◽  
Author(s):  
Koki Kitamura ◽  
Shin-ichi Aota ◽  
Ruriko Sakamoto ◽  
Shun-Ichi Yoshikawa ◽  
Kenji Okazaki
Keyword(s):  
Intracellular Signaling ◽  
Transforming Growth Factor ◽  
Leukemia Cell ◽  
Transcriptional Response ◽  
Erythroid Differentiation ◽  
Transforming Growth Factor Β ◽  
Type I ◽  
Type Ii ◽  
Smad7 Expression ◽  
Ectopic Production

Smad family proteins are essential for transforming growth factor β (TGF-β) signal mediation downstream of a heteromeric complex of the type I and type II receptor serine/threonine kinases. A distant family member, Smad7, is expressed in most mammalian tissues and cells and prevents TGF-β signaling. In this study, we examined the physiologic role of Smad7 in mediating the effects of activin, a member of the TGF-β superfamily of peptides that functions in a number of processes, including blood-cell development. We report here that Smad7 expression is specifically absent in particular hematopoietic cells that respond to activin by differentiating into the erythroid lineage and that ectopic production of Smad7 causes mouse erythroid leukemia (F5-5) cells to become resistant to activin induction of erythroid differentiation. When coexpressed with type I activin receptor ActR-I or ActR-IB in concert with type II receptor ActR-II, Smad7 efficiently reduced an early transcriptional response mediated by ActR-I but had only a minimal effect on the response mediated by ActR-IB. In the presence of Smad7, overexpression of an activated form of ActR-IB, but not of an activated form of ActR-I, induced F5-5 cells to differentiate. These results suggest that Smad7 selectively interferes with the ActR-I pathway in activin signal transduction. The findings also indicate the existence of a novel activity of Smad7 that inhibits erythroid differentiation by blocking intracellular signaling of activin.

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