DRacGAP, a novel Drosophila gene, inhibits EGFR/Ras signalling in the developing imaginal wing disc

Development ◽  
2000 ◽  
Vol 127 (24) ◽  
pp. 5427-5438 ◽  
Author(s):  
S. Sotillos ◽  
S. Campuzano
Keyword(s):  
Maximal Activity ◽  
Wing Disc ◽  
Feedback Mechanism ◽  
Negative Regulator ◽  
Ras Pathway ◽  
Drosophila Gene ◽  
Vein Formation ◽  
Imaginal Wing Disc ◽  
Ras Signalling ◽  
Maximal Expression

We have identified a novel Drosophila gene, DRacGAP, which behaves as a negative regulator of Ρ-family GTPases DRac1 and DCdc42. Reduced function of DRacGAP or increased expression of DRac1 in the wing imaginal disc cause similar effects on vein and sensory organ development and cell proliferation. These effects result from enhanced activity of the EGFR/Ras signalling pathway. We find that in the wing disc, DRac1 enhances EGFR/Ras-dependent activation of MAP Kinase in the prospective veins. Interestingly, DRacGAP expression is negatively regulated by the EGFR/Ras pathway in these regions. During vein formation, local DRacGAP repression would ensure maximal activity of Rac and, in turn, of Ras pathways in vein territories. Additionally, maximal expression of DRacGAP at the vein/intervein boundaries would help to refine the width of the veins. Hence, control of DRacGAP expression by the EGFR/Ras pathway is a previously undescribed feedback mechanism modulating the intensity and/or duration of its signalling during Drosophila development.

Dpp signalling is a key effector of the wing-body wall subdivision of theDrosophilamesothorax

Development ◽  
2002 ◽  
Vol 129 (16) ◽  
pp. 3815-3823 ◽  
Author(s):  
Florencia Cavodeassi ◽  
Isabel Rodríguez ◽  
Juan Modolell
Keyword(s):  
Body Wall ◽  
Larval Instar ◽  
Proximal Part ◽  
Distal Region ◽  
Wing Disc ◽  
Signalling Pathway ◽  
Wing Development ◽  
C Cells ◽  
Imaginal Wing Disc ◽  
Anterior Posterior

During development, the imaginal wing disc of Drosophila is subdivided along the proximal-distal axis into different territories that will give rise to body wall (notum and mesothoracic pleura) and appendage (wing hinge and wing blade). Expression of the Iroquois complex (Iro-C) homeobox genes in the most proximal part of the disc defines the notum, since Iro-C– cells within this territory acquire the identity of the adjacent distal region, the wing hinge. Here we analyze how the expression of Iro-C is confined to the notum territory. Neither Wingless signalling, which is essential for wing development, nor Vein-dependent EGFR signalling, which is needed to activate Iro-C, appear to delimit Iro-C expression. We show that a main effector of this confinement is the TGFβ homolog Decapentaplegic (Dpp), a molecule known to pattern the disc along its anterior-posterior axis. At early second larval instar, the Dpp signalling pathway functions only in the wing and hinge territories, represses Iro-C and confines its expression to the notum territory. Later, Dpp becomes expressed in the most proximal part of the notum and turns off Iro-C in this region. This downregulation is associated with the subdivision of the notum into medial and lateral regions.

PROPERTIES OF PHOSPHATIDYLINOSITOL KINASE IN HUMAN PLATELETS

1987 ◽  
Author(s):  
K Suga ◽  
Y Uemura ◽  
T Tsuijinaka ◽  
M Sakon ◽  
J Kambayashi ◽  
...  
Keyword(s):  
Phosphatidyl Inositol ◽  
Maximal Activity ◽  
Human Platelets ◽  
Feedback Mechanism ◽  
Intracellular Camp ◽  
Pulse Labelling ◽  
Low Concentration ◽  
Phosphatidylinositol Kinase ◽  
Layer Chromatography ◽  
Pi Kinase

We have reported the specific 32P-labelling in phosphatidyl-inositol-4-monophosphate(PIP) of intact platelets upon addition of the agents which elevate intracellular cAMP (Thrombos.Res.44, 155,1986).This event may be catalyzed by the action of Pl-kinase, the properties of which has not been elucidatedyet.Thereby, attempts were made to assay and to characterize PI-kinase of human platelets.Fresh lysed platelets prelabelled with 32P in cold Tris-HCl buffer containing 2mM EGTA were incubated at 37 C in the presence of MgCl2 for designated times and the phospholipids were extracted and analyzed by thin layer chromatography.32P-labelling in PIP was gradually increased in consort with the decreased labelling in PI-4,5-bisphosphate.As the changes in the labelling was not affected by the presence of apyrase and as the radioactive inositol trisphosphate was not detected,it was suggested that the changes is due to the action of phoshomono-esterase rather than PI-kinase or phospholipase C.When 32P-ATP was added to non-labelled lysed platelets upon incubation, 32P was labelled only into PIP and the amount was markedly increased until 5min. after incubation.Since the labelling was strongly inhibited by apyrase,it likely reflects the activity of Pl-kinase. The activity of PI-kinase thus measured required Mg2+ strictly for the activity and the maximal activity was obtained in the presence of 30mM Mg2+ .In contrast,it was markedly inhibited in the presence of Ca2+ (as low as 2mM Ca2+ in the presence of 2mM EGTA),which was compatible.with our previous findings with intact platelets. The activity of A-kinase was not inhibited by a low concentration of Ca2+ .Furthermore,the activity was inhibited by cAMP or dbcAMP in a dose related manner and no enhancement of the activity Was obtained by the addition of catalytic subunit of A-kinase,though a significant reduction in the activity was observed in the presence of inhibitor protein to A-kinase. From these observations,the following conclusions were obtained; l)The activity of Pl-kinase in lysed platelets may be determined by pulse labelling with 32P-ATP. 2)It requires Mg2+ absolutely and is inhibited by a very low concentration of Ca2+. 3)Pl-kinase is activated by A-kinase but the activated enzyme is inhibited by cAMP, suggesting the presence of feedback mechanism.

scholarly journals The Drosophila gene zfh2 is required to establish proximal-distal domains in the wing disc

2008 ◽  
Vol 320 (1) ◽  
pp. 102-112 ◽  
Author(s):  
Javier Terriente ◽  
Daniel Perea ◽  
Magali Suzanne ◽  
Fernando J. Díaz-Benjumea
Keyword(s):  
Wing Disc ◽  
Drosophila Gene

Connecting Hh, Dpp and EGF signalling in patterning of theDrosophilawing; the pivotal role ofcollier/knotin the AP organiser

Development ◽  
2002 ◽  
Vol 129 (18) ◽  
pp. 4261-4269 ◽  
Author(s):  
Michèle Crozatier ◽  
Bruno Glise ◽  
Alain Vincent
Keyword(s):  
Cell Proliferation ◽  
Central Region ◽  
Wing Disc ◽  
Signalling Pathways ◽  
Wild Type ◽  
Drosophila Wing ◽  
Egfr Ligand ◽  
Imaginal Wing Disc ◽  
Primary Determinant ◽  
Dose Dependent

Hedgehog (Hh) signalling from posterior (P) to anterior (A) cells is the primary determinant of AP polarity in the limb field in insects and vertebrates. Hh acts in part by inducing expression of Decapentaplegic (Dpp), but how Hh and Dpp together pattern the central region of the Drosophila wing remains largely unknown. We have re-examined the role played by Collier (Col), a dose-dependent Hh target activated in cells along the AP boundary, the AP organiser in the imaginal wing disc. We found that col mutant wings are smaller than wild type and lack L4 vein, in addition to missing the L3-L4 intervein and mis-positioning of the anterior L3 vein. We link these phenotypes to col requirement for the local upregulation of both emc and N, two genes involved in the control of cell proliferation, the EGFR ligand Vein and the intervein determination gene blistered. We further show that attenuation of Dpp signalling in the AP organiser is also col dependent and, in conjunction with Vein upregulation, required for formation of L4 vein. A model recapitulating the molecular interplay between the Hh, Dpp and EGF signalling pathways in the wing AP organiser is presented.

Transdetermination in imaginal wing disc fragments of Drosophila melanogaster

1983 ◽  
Vol 97 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Brooke S. Kirby ◽  
Peter J. Bryant ◽  
Howard A. Schneiderman
Keyword(s):  
Drosophila Melanogaster ◽  
Wing Disc ◽  
Imaginal Wing Disc
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