Drosophila Lyra Mutations Are Gain-of-Function Mutations of senseless

Genetics ◽  
2001 ◽  
Vol 157 (1) ◽  
pp. 307-315 ◽  
Author(s):  
Riitta Nolo ◽  
Lois A Abbott ◽  
Hugo J Bellen
Keyword(s):  
Apoptotic Cell ◽  
Ectopic Expression ◽  
Wing Disc ◽  
Brdu Incorporation ◽  
Wing Margin ◽  
Aberrant Expression ◽  
Severe Reduction ◽  
Wing Discs ◽  
Necessary And Sufficient ◽  
Wing Pouch

Abstract The Lyra mutation was first described by Jerry Coyne in 1935. Lyra causes recessive pupal lethality and adult heterozygous Lyra mutants exhibit a dominant loss of the anterior and posterior wing margins. Unlike many mutations that cause loss of wing tissue (e.g., scalloped, Beadex, cut, and apterous-Xasta), Lyra wing discs do not exhibit increased necrotic or apoptotic cell death, nor do they show altered BrdU incorporation. However, during wing disc eversion, loss of the anterior and posterior wing margins is apparent. We have previously shown that senseless, a gene that is necessary and sufficient for peripheral nervous system (PNS) development, is allelic to Lyra. Here we show by several genetic criteria that Lyra alleles are neomorphic alleles of senseless that cause ectopic expression of SENSELESS in the wing pouch. Similarly, overexpression of SENSELESS in the wing disc causes loss of wing margin tissue, thereby mimicking the Lyra phenotype. Lyra mutants display aberrant expression of DELTA, VESTIGIAL, WINGLESS, and CUT. As in Lyra mutants, overexpression of SENSELESS in some areas of the wing pouch also leads to loss of WINGLESS and CUT. In summary, our data indicate that overexpression of SENSELESS causes a severe reduction in NOTCH signaling that in turn may lead to decreased transcription of several key genes required for wing development, leading to a failure in cell proliferation and loss of wing margin tissue.

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.

Role of the EGF receptor pathway in growth and patterning of the Drosophila wing through the regulation of vestigial

Development ◽  
1999 ◽  
Vol 126 (5) ◽  
pp. 975-985 ◽  
Author(s):  
R. Nagaraj ◽  
A.T. Pickup ◽  
R. Howes ◽  
K. Moses ◽  
M. Freeman ◽  
...  
Keyword(s):  
Egf Receptor ◽  
Regulatory Gene ◽  
Ectopic Expression ◽  
Wing Disc ◽  
Loss Of Function ◽  
Drosophila Wing ◽  
Expression Studies ◽  
Coordinated Expression ◽  
Wing Pouch

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.

scholarly journals Autonomous termination of proliferation in the Drosophila wing disc is TORC1 dependent

2020 ◽  
Author(s):  
Katrin Strassburger ◽  
Marilena Lutz ◽  
Sandra Müller ◽  
Aurelio A. Teleman
Keyword(s):  
Experimental Manipulation ◽  
Wing Disc ◽  
Wing Size ◽  
Final Size ◽  
Drosophila Wing ◽  
Adult Wing ◽  
Wing Discs ◽  
Underlying Mechanisms ◽  
Constant Growth ◽  
Wing Pouch

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.

Serrate-mediated activation of Notch is specifically blocked by the product of the gene fringe in the dorsal compartment of the Drosophila wing imaginal disc

Development ◽  
1997 ◽  
Vol 124 (15) ◽  
pp. 2973-2981 ◽  
Author(s):  
R.J. Fleming ◽  
Y. Gu ◽  
N.A. Hukriede
Keyword(s):  
Imaginal Disc ◽  
Ectopic Expression ◽  
Wing Disc ◽  
Specific Response ◽  
Wing Margin ◽  
Drosophila Wing ◽  
Imaginal Wing Disc ◽  
Dorsoventral Boundary ◽  
Drosophila Cells ◽  
Notch Ligands

In the developing imaginal wing disc of Drosophila, cells at the dorsoventral boundary require localized Notch activity for specification of the wing margin. The Notch ligands Serrate and Delta are required on opposite sides of the presumptive wing margin and, even though activated forms of Notch generate responses on both sides of the dorsoventral boundary, each ligand generates a compartment-specific response. In this report we demonstrate that Serrate, which is expressed in the dorsal compartment, does not signal in the dorsal regions due to the action of the fringe gene product. Using ectopic expression, we show that regulation of Serrate by fringe occurs at the level of protein and not Serrate transcription. Furthermore, replacement of the N-terminal region of Serrate with the corresponding region of Delta abolishes the ability of fringe to regulate Serrate without altering Serrate-specific signaling.

scholarly journals Phenotypic and molecular characterization of SerD, a dominant allele of the Drosophila gene Serrate.

Genetics ◽  
1995 ◽  
Vol 139 (1) ◽  
pp. 203-213 ◽  
Author(s):  
U Thomas ◽  
F Jönsson ◽  
S A Speicher ◽  
E Knust
Keyword(s):  
Transmembrane Protein ◽  
Ectopic Expression ◽  
Rna Degradation ◽  
Wing Margin ◽  
Edge Zone ◽  
Drosophila Gene ◽  
Epidermal Growth ◽  
Wing Discs ◽  
Third Instar Larvae

Abstract The Drosophila gene Serrate (Ser) encodes a transmembrane protein with 14 epidermal growth factor--like repeats in its extracellular domain, which is required for the control of cell proliferation and pattern formation during wing development. Flies hetero- or homozygous for the dominant mutation SerD exhibit scalloping of the wing margin due to cell death during pupal stages. SerD is associated with an insertion of the transposable element Tirant in the 3' untranslated region of the gene, resulting in the truncation of the Ser RNA, thereby eliminating putative RNA degradation signals located further downstream. This leads to increased stability of Ser RNA and higher levels of Serrate protein. In wing discs of wild-type third instar larvae, the Serrate protein exhibits a complex expression pattern, including a strong stripe dorsal and a weaker stripe ventral to the prospective wing margin. Wing discs of SerD third instar larvae exhibit additional Serrate protein expression in the edge zone of the future wing margin, where it is normally not detectable. In these cells expression of wing margin specific genes, such as cut and wingless, is repressed. By using the yeast Gal4 system to induce locally restricted ectopic expression of Serrate in the edge zone of the prospective wing margin, we can reproduce all aspects of the SerD wing phenotype, that is, repression of wing margin-specific genes, scalloping of the wing margin and enhancement of the Notch haplo-insufficiency wing phenotype. This suggests that expression of the Serrate protein in the cells of the edge zone of the wing margin, where it is normally absent, interferes with the proper development of the margin.

scholarly journals Bab2 activates JNK signaling to reprogram Drosophila wing disc development

2020 ◽  
Author(s):  
Yunpo Zhao ◽  
Jianli Duan ◽  
Alexis Dziedziech ◽  
Sabrina Büttner ◽  
Ylva Engström
Keyword(s):  
Transcription Factor ◽  
Cellular Proliferation ◽  
Apoptotic Cell ◽  
Wing Disc ◽  
Surrounding Tissue ◽  
Dependent Manner ◽  
Posterior Compartment ◽  
Jnk Signaling ◽  
Compensatory Proliferation ◽  
Wing Discs

AbstractIn response to cellular stress and damage, certain tissues are able to regenerate and to restore tissue homeostasis. In Drosophila imaginal wing discs, dying cells express mitogens that induce compensatory proliferation in the surrounding tissue. Here we report that high levels of the BTB/POZ transcription factor Bab2 in the posterior compartment of wing discs activates c-Jun N-terminal kinase (JNK) signaling and local, cell-autonomous apoptotic cell death. This in turn triggered the upregulation of the Dpp mitogen and cellular proliferation in the anterior compartment in a JNK-dependent manner. In the posterior compartment, however, dpp expression was suppressed, most likely by direct transcriptional repression by Bab2. This dual-mode of JNK-signaling, autocrine pro-apoptotic signaling and paracrine pro-proliferative signaling, led to opposite effects in the two compartments and reprogramming of the adult wing structure. We establish Bab2 as a regulator of wing disc development, with the capacity to reprogram development via JNK activation in a cell-autonomous and non-cell-autonomous manner.Summary statementZhao et al. shows that the BTB/POZ transcription factor Bab2 is a potent activator of JNK signaling, apoptosis and compensatory proliferation, thereby driving both pro-tumorigenic and anti-tumorigenic processes.

Antigene and Antiproliferative Effects of Triplex-Forming Oligonucleotide (TFO) Targeted on hmgb1 Gene in Human Hepatoma Cells

2020 ◽  
Vol 20 (16) ◽  
pp. 1943-1955
Author(s):  
Neelam Lohani ◽  
Moganty R. Rajeswari
Keyword(s):  
Apoptotic Cell ◽  
Isothermal Calorimetry ◽  
High Mobility ◽  
Rational Drug Design ◽  
Human Hepatoma Cells ◽  
Aberrant Expression ◽  
Bioinformatic Tools ◽  
Hmgb1 Expression ◽  
Dna Triplex ◽  
Triplex Forming Oligonucleotide

Background: The high mobility group box 1 (hmgb1) is one of the frequently over-expressed genes whose aberrant expression is reported in a number of human cancers. Various strategies are underway to inhibit hmgb1 expression in cancer cells having considerable therapeutic value. Objective: The present work involves selective transcriptional inhibition of the hmgb1 gene using selective DNA triplex structure-based gene technology. Here, the promoter region of the hmgb1 gene at position (-183 to -165) from the transcription start site as a target was selected using bioinformatic tools. Methods: The DNA triplex formation by the DNA of the target gene and TFO was confirmed using UV absorption spectroscopy, Circular Dichroism, and Isothermal Calorimetry. Results: Treatment of HepG2 cell with specific Triplex-forming Oligonucleotide significantly downregulated HMGB1 expression level at mRNA and protein levels by 50%, while the classical anticancer drugs, actinomycin/ adriamycin as positive controls showed 65% and the combination of TFO and drug decreased by 70%. The anti-proliferative effects of TFO correlated well with the fact of accumulation of cells in the Go phase and apoptotic cell death. Further, the binding of anti-cancer drugs to hmgb1 is stronger in DNA triplex state as compared to hmgb1 alone, suggesting the combination therapy as a better option. Conclusion: Therefore, the ability of hmgb1 targeted triplex-forming oligonucleotide in combination with triplex selective anticancer drug holds promise in the treatment of malignancies associated with hmgb1 overexpression. The result obtained may open up new vistas to provide a basis for the rational drug design and searching for high-affinity ligands with a high triplex selectivity.

scholarly journals Cytoplasmic condensation is both necessary and sufficient to induce apoptotic cell death

2008 ◽  
Vol 121 (3) ◽  
pp. 290-297 ◽  
Author(s):  
N. J. Ernest ◽  
C. W. Habela ◽  
H. Sontheimer
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Necessary And Sufficient

Positional signaling by hedgehog in Drosophila imaginal disc development

Development ◽  
1995 ◽  
Vol 121 (1) ◽  
pp. 1-10 ◽  
Author(s):  
A.L. Felsenfeld ◽  
J.A. Kennison
Keyword(s):  
Hedgehog Signaling ◽  
Imaginal Disc ◽  
Ectopic Expression ◽  
Posterior Compartment ◽  
Anterior Compartment ◽  
Segment Polarity ◽  
Wing Structures ◽  
Wing Discs ◽  
Segment Polarity Gene ◽  
Polarity Gene

We describe a dominant gain-of-function allele of the segment polarity gene hedgehog. This mutation causes ectopic expression of hedgehog mRNA in the anterior compartment of wing discs, leading to overgrowth of tissue in the anterior of the wing and partial duplication of distal wing structures. The posterior compartment of the wing is unaffected. Other imaginal derivatives are affected, resulting in duplications of legs and antennae and malformations of eyes. In mutant imaginal wing discs, expression of the decapentaplegic gene, which is implicated in the hedgehog signaling pathway, is also perturbed. The results suggest that hedgehog protein acts in the wing as a signal to instruct neighboring cells to adopt fates appropriate to the region of the wing just anterior to the compartmental boundary.

hlh-12, a gene that is necessary and sufficient to promote migration of gonadal regulatory cells in C. elegans, evolved within the Caenorhabditis clade

Genetics ◽  
2021 ◽  
Author(s):  
Hana E Littleford ◽  
Karin Kiontke ◽  
David H A Fitch ◽  
Iva Greenwald
Keyword(s):  
Ectopic Expression ◽  
Morphological Diversity ◽  
Nematode Species ◽  
Bhlh Protein ◽  
Vulval Development ◽  
C Elegans ◽  
Form And Function ◽  
Somatic Gonad ◽  
And Function ◽  
Necessary And Sufficient

Abstract Specialized cells of the somatic gonad primordium of nematodes play important roles in the final form and function of the mature gonad. C. elegans hermaphrodites are somatic females that have a two-armed, U-shaped gonad that connects to the vulva at the midbody. The outgrowth of each gonad arm from the somatic gonad primordium is led by two female Distal Tip Cells (fDTC), while the Anchor Cell (AC) remains stationary and central to coordinate uterine and vulval development. The bHLH protein HLH-2 and its dimerization partners LIN-32 and HLH-12 had previously been shown to be required for fDTC specification. Here, we show that ectopic expression of both HLH-12 and LIN-32 in cells with AC potential transiently transforms them into fDTC-like cells. Furthermore, hlh-12 was known to be required for the fDTCs to sustain gonad arm outgrowth. Here, we show that ectopic expression of HLH-12 in the normally stationary AC causes displacement from its normal position, and that displacement likely results from activation of the leader program of fDTCs because it requires genes necessary for gonad arm outgrowth. Thus, HLH-12 is both necessary and sufficient to promote gonadal regulatory cell migration. As differences in female gonadal morphology of different nematode species reflect differences in the fate or migratory properties of the fDTCs or of the AC, we hypothesized that evolutionary changes in the expression of hlh-12 may underlie evolution of such morphological diversity. However, we were unable to identify an hlh-12 ortholog outside of Caenorhabditis. Instead, by performing a comprehensive phylogenetic analysis of all Class II bHLH proteins in multiple nematode species, we found that HLH-12 evolved within the Caenorhabditis clade, possibly by duplicative transposition of hlh-10. Our analysis suggests that control of gene regulatory hierarchies for gonadogenesis can be remarkably plastic during evolution without adverse phenotypic consequence.

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