scholarly journals Ecdysone regulates Drosophila wing disc size via a TORC1 dependent mechanism

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Katrin Strassburger ◽  
Marilena Lutz ◽  
Sandra Müller ◽  
Aurelio A. Teleman

AbstractMost cells in a developing organ stop proliferating when the organ reaches a correct, final size. The underlying molecular mechanisms are not understood. We find that in Drosophila the hormone ecdysone controls wing disc size. To study how ecdysone affects wing size, we inhibit endogenous ecdysone synthesis and feed larvae exogenous ecdysone in a dose-controlled manner. For any given ecdysone dose, discs stop proliferating at a particular size, with higher doses enabling discs to reach larger sizes. Termination of proliferation coincides with a drop in TORC1, but not Dpp or Yki signaling. Reactivating TORC1 bypasses the termination of proliferation, indicating that TORC1 is a main downstream effector causing proliferation termination at the maximal ecdysone-dependent size. Experimental manipulation of Dpp or Yki signaling can bypass proliferation termination in hinge and notum regions, but not the pouch, suggesting that the mechanisms regulating proliferation termination may be distinct in different disc regions.

2020 ◽  
Author(s):  
Katrin Strassburger ◽  
Marilena Lutz ◽  
Sandra Müller ◽  
Aurelio A. Teleman

AbstractCells in a developing organ stop proliferating when the organ reaches a correct, final size. The underlying mechanisms are not understood. Although many signaling pathways and cell cycle components are required to sustain cell proliferation, which one of these turns off to terminate proliferation is not known. Here we study proliferation termination using Drosophila wing discs. We extend larval development to provide wing discs a constant growth-sustaining environment, allowing them to terminate proliferation autonomously. We find that the wing pouch, which forms the adult wing blade, terminates proliferation in the absence of brinker or warts, indicating that neither Dpp signaling nor Hippo/Yorkie signaling control final wing size. Instead, termination of proliferation coincides with reduced TORC1 activity and is bypassed by reactivating TORC1. Hence proliferation ceases due to reduced cell growth. Experimental manipulation of Dpp or Yki signaling can bypass proliferation termination in hinge and notum regions, suggesting that the mechanisms regulating proliferation termination may be distinct in different regions of the disc.One Sentence SummaryUsing Drosophila, Strassburger et al. investigate the termination of proliferation of an organ when it reaches its final size, and show this occurs due to a drop in TORC1 signaling.


Author(s):  
J.S. Ryerse

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.


Development ◽  
1981 ◽  
Vol 66 (1) ◽  
pp. 117-126
Author(s):  
Jane Karlsson ◽  
R. J. Smith

It is a general rule that of two complementary Drosophila imaginal disc fragments, one regenerates and the other duplicates. This paper reports an investigation of an exception to this rule. Duplicating fragments from the periphery of the wing disc which lacked presumptive notum were found to regenerate notum structures during and after duplication. The propensity for this was greatest in fragments lying close to the presumptive notum, with the exception of a fragment confined to the posterior compartment, which did not regenerate notum. Structures were added sequentially, and regeneration stopped once most of the notum was present. These results are not easily explained by the polar coordinate model, which states that regeneration cannot occur from duplicating fragments. Since compartments appear to be involved in this type of regeneration as in others, it is suggested that a new type of model is required, one which permits simultaneous regeneration and duplication, and assigns a major role to compartments.


2016 ◽  
Vol 113 (45) ◽  
pp. E6993-E7002 ◽  
Author(s):  
Anupama Hemalatha ◽  
Chaitra Prabhakara ◽  
Satyajit Mayor

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.


2021 ◽  
Vol 221 (1) ◽  
Author(s):  
Jun Zhou ◽  
Yasamin Dabiri ◽  
Rodrigo A. Gama-Brambila ◽  
Shahrouz Ghafoory ◽  
Mukaddes Altinbay ◽  
...  

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.


1994 ◽  
Vol 197 (1) ◽  
pp. 377-391 ◽  
Author(s):  
K R Prier ◽  
O H Beckman ◽  
N J Tublitz

The central nervous system of the moth Manduca sexta contains a group of myoregulatory neuropeptides, the CAPs (Cardioacceleratory Peptides), which cause a physiologically important, dose-dependent increase in heart rate during wing inflation and flight in adult moths. We report here that the response of the adult heart to a subset of the CAPs, the CAP2S, is potentiated nearly twofold in the chronic presence of subthreshold levels of the biogenic amine octopamine or near-threshold levels of the biogenic amine serotonin. Subthreshold levels of the CAP2S fail to alter the response of the heart to octopamine. We have begun to investigate the molecular mechanisms underlying this potentiation. Previous work on the adult heart has shown that the CAP2s act through an inositol-1,4,5-trisphosphate second-messenger system. Here, we demonstrate that the cardioexcitatory effects of the two amines, in contrast to those of the CAP2S, are both mediated by cyclic AMP. Application to the heart of either 10(-5) moll-1 octopamine or 10(-6)moll-1 serotonin elicits a threefold increase in intracellular cyclic AMP levels. The CAP2S have no effect on cyclic AMP levels in the heart. These results illustrate a mechanism by which the effectiveness of a neurohormone can be increased with minimal cost to the animal. In Manduca sexta, subthreshold levels of octopamine are found in the haemolymph during wing inflation and flight. Thus, it is possible that octopamine up-regulates the effects of CAP2 via a cyclic-AMP-dependent mechanism during these activities.


Development ◽  
1999 ◽  
Vol 126 (5) ◽  
pp. 975-985 ◽  
Author(s):  
R. Nagaraj ◽  
A.T. Pickup ◽  
R. Howes ◽  
K. Moses ◽  
M. Freeman ◽  
...  

Growth and patterning of the Drosophila wing disc depends on the coordinated expression of the key regulatory gene vestigial both in the Dorsal-Ventral (D/V) boundary cells and in the wing pouch. We propose that a short-range signal originating from the core of the D/V boundary cells is responsible for activating EGFR in a zone of organizing cells on the edges of the D/V boundary. Using loss-of-function mutations and ectopic expression studies, we show that EGFR signaling is essential for vestigial transcription in these cells and for making them competent to undergo subsequent vestigial-mediated proliferation within the wing pouch.


Sign in / Sign up

Export Citation Format

Share Document