Hedgehog activity, independent of decapentaplegic, participates in wing disc patterning

Development ◽  
1997 ◽  
Vol 124 (6) ◽  
pp. 1227-1237 ◽  
Author(s):  
J.L. Mullor ◽  
M. Calleja ◽  
J. Capdevila ◽  
I. Guerrero
Keyword(s):  
Zinc Finger ◽  
Imaginal Disc ◽  
Zinc Finger Protein ◽  
Ectopic Expression ◽  
Wing Disc ◽  
Signal Molecule ◽  
Cubitus Interruptus ◽  
Drosophila Wing ◽  
Finger Protein

In the Drosophila wing imaginal disc, the Hedgehog (Hh) signal molecule induces the expression of decapentaplegic (dpp) in a band of cells abutting the anteroposterior (A/P) compartment border. It has been proposed that Dpp organizes the patterning of the entire wing disc. We have tested this proposal by studying the response to distinct levels of ectopic expression of Hh and Dpp, using the sensory organ precursors (SOPs) of the wing and notum and the presumptive wing veins as positional markers. Here, we show that Dpp specifies the position of most SOPs in the notum and of some of them in the wing. Close to the A/P compartment border, however, SOPs are specified by Hh rather than by Dpp alone. We also show that late signaling by Hh, after setting up dpp expression, is responsible for the formation of vein 3 and the scutellar region, and also for the determination of the distance between veins 3 and 4. One of the genes that mediates the Hh signal is the zinc-finger protein Cubitus interruptus (Ci). These results indicate that Hh has a Dpp-independent morphogenetic effect in the region of the wing disc near the A/P border.

Control of growth and patterning of the Drosophila wing imaginal disc by EGFR-mediated signaling

Development ◽  
2002 ◽  
Vol 129 (6) ◽  
pp. 1369-1376 ◽  
Author(s):  
Myriam Zecca ◽  
Gary Struhl
Keyword(s):  
Gene Expression ◽  
Imaginal Disc ◽  
Ectopic Expression ◽  
Growth Factor Receptor ◽  
Wing Disc ◽  
Wing Imaginal Disc ◽  
Egfr Signaling ◽  
Drosophila Wing ◽  
Compartment Boundary ◽  
Egfr Ligand

The subdivision of the Drosophila wing imaginal disc into dorsoventral (DV) compartments and limb-body wall (wing-notum) primordia depends on Epidermal Growth Factor Receptor (EGFR) signaling, which heritably activates apterous (ap) in D compartment cells and maintains Iroquois Complex (Iro-C) gene expression in prospective notum cells. We examine the source, identity and mode of action of the EGFR ligand(s) that specify these subdivisions. Of the three known ligands for the Drosophila EGFR, only Vein (Vn), but not Spitz or Gurken, is required for wing disc development. We show that Vn activity is required specifically in the dorsoproximal region of the wing disc for ap and Iro-C gene expression. However, ectopic expression of Vn in other locations does not reorganize ap or Iro-C gene expression. Hence, Vn appears to play a permissive rather than an instructive role in organizing the DV and wing-notum segregations, implying the existance of other localized factors that control where Vn-EGFR signaling is effective. After ap is heritably activated, the level of EGFR activity declines in D compartment cells as they proliferate and move ventrally, away from the source of the instructive ligand. We present evidence that this reduction is necessary for D and V compartment cells to interact along the compartment boundary to induce signals, like Wingless (Wg), which organize the subsequent growth and differentiation of the wing primordium.

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 The tumor suppressor Zinc finger protein 471 suppresses breast cancer growth and metastasis through inhibiting AKT and Wnt/β-catenin signaling

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Chunfang Tao ◽  
Juan Luo ◽  
Jun Tang ◽  
Danfeng Zhou ◽  
Shujun Feng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Tumor Cell ◽  
Zinc Finger ◽  
Molecular Mechanisms ◽  
Zinc Finger Protein ◽  
Ectopic Expression ◽  
Surgical Margin ◽  
Mesenchymal Transition ◽  
Finger Protein

Abstract Background Zinc-finger protein 471 (ZNF471) is a member of the Krüppel-associated box domain zinc finger protein (KRAB-ZFP) family. ZNF471 is methylated in squamous cell carcinomas of tongue, stomach and esophageal. However, its role in breast carcinogenesis remains elusive. Here, we studied its expression, functions, and molecular mechanisms in breast cancer. Methods We examined ZNF471 expression by RT-PCR and qPCR. Methylation-specific PCR determined its promoter methylation. Its biological functions and related molecular mechanisms were assessed by CCK-8, clonogenicity, wound healing, Transwell, nude mice tumorigenicity, flow cytometry, BrdU-ELISA, immunohistochemistry and Western blot assays. Results ZNF471 was significantly downregulated in breast cell lines and tissues due to its promoter CpG methylation, compared with normal mammary epithelial cells and paired surgical-margin tissues. Ectopic expression of ZNF471 substantially inhibited breast tumor cell growth in vitro and in vivo, arrested cell cycle at S phase, and promoted cell apoptosis, as well as suppressed metastasis. Further knockdown of ZNF471 verified its tumor-suppressive effects. We also found that ZNF471 exerted its tumor-suppressive functions through suppressing epithelial-mesenchymal transition, tumor cell stemness and AKT and Wnt/β-catenin signaling. Conclusions ZNF471 functions as a tumor suppressor that was epigenetically inactivated in breast cancer. Its inhibition of AKT and Wnt/β-catenin signaling pathways is one of the mechanisms underlying its anti-cancer effects.

scholarly journals Isolation of a cDNA clone encoding a zinc finger protein highly expressed in T-leukemia lines

Blood ◽  
1992 ◽  
Vol 80 (10) ◽  
pp. 2571-2576 ◽  
Author(s):  
BY Wu ◽  
EW Hanley ◽  
LA Turka ◽  
GJ Nabel
Keyword(s):  
Zinc Finger ◽  
Cdna Clone ◽  
Messenger Rna ◽  
Zinc Finger Protein ◽  
Leukemia Cell ◽  
Lymphoid Cells ◽  
Gap Gene ◽  
Finger Protein ◽  
Leukemia Cell Lines

Abstract A cDNA clone encoding a novel zinc finger protein expressed in lymphoid cells has been isolated. This protein contains 5 repeats of the C2H2 motif previously described in the Drosophila gap gene, Kruppel, which is involved in embryo segmentation. Northern blot analysis showed that the messenger RNA (mRNA) encoding this protein is expressed at high levels in a variety of T-leukemia cell lines, at lower levels in some B cells, but is not observed in nonlymphoid cells. Within the T lineage, the mRNA is found at high levels in both alpha beta and gamma delta T cells. These data suggest that this cDNA, designated Hkr-T1, represents a gene that may contribute to the determination of the differentiation and the specificity within lymphoid cells.

Regulation of Drosophila wing vein patterning: net encodes a bHLH protein repressing rhomboid and is repressed by rhomboid-dependent Egfr signalling

Development ◽  
2000 ◽  
Vol 127 (21) ◽  
pp. 4729-4741 ◽  
Author(s):  
D. Brentrup ◽  
H. Lerch ◽  
H. Jackle ◽  
M. Noll
Keyword(s):  
Imaginal Disc ◽  
Egf Receptor ◽  
Ectopic Expression ◽  
Wing Disc ◽  
Bhlh Protein ◽  
Wing Vein ◽  
Drosophila Wing ◽  
Vein Formation ◽  
Mutual Repression ◽  
Vein Patterning

The stereotyped pattern of veins in the Drosophila wing is generated in response to local EGF signalling. Mutations in the rhomboid (rho) gene, which encodes a sevenpass membrane protein required to enhance signalling transmitted by the EGF receptor (Egfr), inhibit vein development and disrupt the vein pattern. By contrast, net mutations produce ectopic veins in intervein regions. We have cloned the net gene and show that it encodes a basic HLH protein that probably acts as a transcriptional repressor. net and rho are expressed in mutually exclusive patterns during the development of the wing imaginal disc. Lack of net activity causes rho expression to expand, and vice versa. Furthermore, ectopic expression of net or rho results in their mutual repression and thus suppresses vein formation or generates tube-like wings composed of vein-like tissue. Egfr signalling and net exert mutually antagonising activities during the specification of vein versus intervein fate. While Egfr signalling represses net transcription, net exhibits a two-tiered control by repressing rho transcription and interfering with Egfr signalling downstream of Rho. Our results further suggest that net is required to maintain intervein development by restricting Egfr signalling, which promotes vein development, to the Net-free vein regions of the wing disc.

Drumstick is a zinc finger protein that antagonizes Lines to control patterning and morphogenesis of theDrosophilahindgut

Development ◽  
2002 ◽  
Vol 129 (15) ◽  
pp. 3645-3656 ◽  
Author(s):  
Ryan B. Green ◽  
Victor Hatini ◽  
Katherine A. Johansen ◽  
Xue-Jun Liu ◽  
Judith A. Lengyel
Keyword(s):  
Gene Expression ◽  
Small Intestine ◽  
Amino Acid ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Ectopic Expression ◽  
Genetic Data ◽  
Specific Pattern ◽  
Cell Rearrangement ◽  
Finger Protein

Elongation of the Drosophila embryonic hindgut epithelium occurs by a process of oriented cell rearrangement requiring the genes drumstick (drm) and lines (lin). The elongating hindgut becomes subdivided into domains – small intestine, large intestine and rectum – each characterized by a specific pattern of gene expression dependent upon normal drm and lin function. We show that drm encodes an 81 amino acid (10 kDa) zinc finger protein that is a member of the Odd-skipped family. drm expression is localized to the developing midgut-hindgut junction and is required to establish the small intestine, while lin is broadly expressed throughout the gut primordium and represses small intestine fate. lin is epistatic to drm, suggesting a model in which localized expression of drm blocks lin activity, thereby allowing small intestine fate to be established. Further supporting this model, ectopic expression of Drm throughout the hindgut produces a lin phenotype. Biochemical and genetic data indicate that the first conserved zinc finger of Drm is essential for its function. We have thus defined a pathway in which a spatially localized zinc finger protein antagonizes a globally expressed protein, thereby leading to specification of a domain (the small intestine) necessary for oriented cell rearrangement.

The differentiation of the serotonergic neurons in the Drosophila ventral nerve cord depends on the combined function of the zinc finger proteins Eagle and Huckebein

Development ◽  
1997 ◽  
Vol 124 (13) ◽  
pp. 2515-2525 ◽  
Author(s):  
R. Dittrich ◽  
T. Bossing ◽  
A.P. Gould ◽  
G.M. Technau ◽  
J. Urban
Keyword(s):  
Cell Fate ◽  
Zinc Finger ◽  
Nerve Cord ◽  
Ventral Nerve Cord ◽  
Zinc Finger Protein ◽  
Ectopic Expression ◽  
Cell Lineage ◽  
Lineage Tracing ◽  
Serotonergic Neurons ◽  
Finger Protein

The Drosophila ventral nerve cord (vNC) derives from a stereotyped population of neural stem cells, neuroblasts (NBs), each of which gives rise to a characteristic cell lineage. The mechanisms leading to the specification and differentiation of these lineages are largely unknown. Here we analyse mechanisms leading to cell differentiation within the NB 7–3 lineage. Analogous to the grasshopper, NB 7–3 is the progenitor of the Drosophila vNC serotonergic neurons. The zinc finger protein Eagle (Eg) is expressed in NB 7–3 just after delamination and is present in all NB 7–3 progeny until late stage 17. DiI cell lineage tracing and immunocytochemistry reveal that eg is required for normal pathfinding of interneuronal projections and for restricting the cell number in the thoracic NB 7–3 lineage. Moreover, eg is required for serotonin expression. Ectopic expression of Eg protein forces specific additional CNS cells to enter the serotonergic differentiation pathway. Like NB 7–3, the progenitor(s) of these ectopic cells express Huckebein (Hkb), another zinc finger protein. However, their progenitors do not express engrailed (en) as opposed to the NB 7–3 lineage, where en acts upstream of eg. We conclude that eg and hkb act in concert to determine serotonergic cell fate, while en is more distantly involved in this process by activating eg expression. Thus, we provide the first functional evidence for a combinatorial code of transcription factors acting early but downstream of segment polarity genes to specify a unique neuronal cell fate.

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