The roles of hedgehog and engrailed in patterning adult abdominal segments of Drosophila

Development ◽  
1997 ◽  
Vol 124 (19) ◽  
pp. 3703-3714 ◽  
Author(s):  
A. Kopp ◽  
M.A. Muskavitch ◽  
I. Duncan
Keyword(s):  
Ectopic Expression ◽  
Restrictive Temperature ◽  
Primary Role ◽  
Loss Of Function ◽  
Posterior Compartment ◽  
Anterior Portion ◽  
Posterior Portion ◽  
Anterior Compartment ◽  
Present Evidence ◽  
Anterior Patterning

We present evidence that hedgehog (hh) protein secreted by posterior compartment cells plays a key role in patterning the posterior portion of the anterior compartment in adult abdominal segments. Loss of function of hh in the hh(ts2) mutant causes the loss of posterior tergite characteristics in the anterior compartment, whereas ectopic expression driven by hs-hh or the gain-of-function allele hh(Mir) causes transformation of anterior structures toward the posterior. FLP-out hh-expressing clones in the anterior compartment induce surrounding wild-type cells to produce posterior tergite structures, establishing that hh functions nonautonomously. The effects of pulses of ectopic expression driven by hs-hh indicate that bristle type and pigmentation are patterned by hh at widely different times in pupal development. We also present evidence that the primary polarization of abdominal segments is symmetric. This symmetry is strikingly revealed by ectopic expression of engrailed (en). As expected, this transforms anterior compartment cells to posterior compartment identity. In addition, however, ectopic en expression causes an autonomous reversal of polarity in the anterior portion of the anterior compartment, but not the posterior portion. By determining the position of polarity reversal within en-expressing clones, we were able to define a cryptic line of symmetry that lies within the pigment band of the normal tergite. This line appears to be retained in hh(ts2) mutants raised at the restrictive temperature, suggesting it is not established by hh signaling. We argue that the primary role of hh in controlling polarity is to cause anterior compartment cells to reverse their interpretation of an underlying symmetric polarization. Consistent with this, we find that strong ectopic expression of hh causes mirror-symmetric double posterior patterning, whereas hh loss of function can cause mirror-symmetric double anterior patterning.

scholarly journals Control of cell fate and polarity in the adult abdominal segments of Drosophila by optomotor-blind

Development ◽  
1997 ◽  
Vol 124 (19) ◽  
pp. 3715-3726 ◽  
Author(s):  
A. Kopp ◽  
I. Duncan
Keyword(s):  
Cell Fate ◽  
Anterior Part ◽  
Ectopic Expression ◽  
Mirror Image ◽  
Posterior Compartment ◽  
Anterior Portion ◽  
Posterior Portion ◽  
Anterior Compartment ◽  
Compartment Boundary ◽  
Hh Signaling

In an accompanying report (Kopp, A., Muskavitch, M. A. T. and Duncan, I. (1997) Development 124, 3703–3714), we show that Hh protein secreted by posterior compartment cells patterns the posterior portion of the anterior compartment in adult abdominal segments. Here we show that this function of hh is mediated by optomotor-blind (omb). omb- mutants mimic the effects of loss-of-function alleles of hh: structures from the posterior of the anterior compartment are lost, and often this region develops as a mirror image of the anterior portion. Structures from the anterior part of the posterior compartment are also lost. In the pupa, omb expression in abdominal histoblasts is highest at or near the compartment boundary, and decreases in a shallow gradient toward the anterior. This gradient is due to activation of omb by Hh secreted by posterior compartment cells. In contrast to imaginal discs, this Hh signaling is not mediated by dpp or wg. We describe several gain-of-function alleles that cause ectopic expression of omb in the anterior of the segment. Most of these cause the anterior region to develop with posterior characteristics without affecting polarity. However, an allele that drives high level ubiquitous expression of omb (QdFab) causes the anterior tergite to develop as a mirror-image duplication of the posterior tergite, a pattern opposite to that seen in omb- mutants. Ubiquitous expression of hh causes similar double-posterior patterning. We find that omb- alleles suppress this effect of ectopic hh expression and that posterior patterning becomes independent of hh in the QdFab mutant. These observations indicate that omb is the primary target of hh signaling in the adult abdomen. However, it is clear that other targets exist. One of these is likely Scruffy, a novel gene that we describe, which acts in parallel to omb. To explain the effects of omb alleles, we propose that both anterior and posterior compartments in the abdomen are polarized by underlying symmetric gradients of unknown origin. We suggest that omb has two functions. First, it specifies the development of appropriate structures both anterior and posterior to the compartment boundary. Second, it causes cells to reverse their interpretation of polarity specified by the underlying symmetric gradients.

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.

Roles of wingless in patterning the larval epidermis of Drosophila

Development ◽  
1991 ◽  
Vol 113 (2) ◽  
pp. 471-485 ◽  
Author(s):  
A. Bejsovec ◽  
A. Martinez Arias
Keyword(s):  
Gene Product ◽  
Epidermal Cells ◽  
Stable Expression ◽  
Gene Products ◽  
Anterior Portion ◽  
Posterior Portion ◽  
Present Evidence ◽  
Larval Cuticle ◽  
Cuticular Structures

The larval epidermis of Drosophila shows a stereotyped segmentally repeating pattern of cuticular structures. Mutants deficient for the wingless gene product show highly disrupted patterning of the larval cuticle. We have manipulated expression of the wg gene product to assess its role in this patterning process. We present evidence for four distinct phases of wg function in epidermal cells: (1) an early requirement in engrailed-expressing cells to establish and maintain stable expression of en, (2) a discrete period when wg and en gene products act in concert to generate positional values in the anterior portion of the ventral segment and all values of the dorsal and lateral epidermis, (3) a progressive function (dependent on prior interaction with the en-expressing cells) in conferring positional values to cells within the posterior portion of the segment, and (4) a late continuous requirement for maintaining some ventral positional values.

scholarly journals Effect of abx, bx and pbx mutations on expression of homeotic genes in Drosophila larvae.

Genetics ◽  
1990 ◽  
Vol 124 (4) ◽  
pp. 899-908 ◽  
Author(s):  
J W Little ◽  
C A Byrd ◽  
D L Brower
Keyword(s):  
Ectopic Expression ◽  
Wing Disc ◽  
Homeotic Genes ◽  
Wild Type ◽  
Posterior Compartment ◽  
Altered Expression ◽  
Anterior Compartment ◽  
Regulatory Domains ◽  
Wild Type Phenotype ◽  
Drosophila Larvae

Abstract We have examined the patterns of expression of the homeotic gene Ubx in imaginal discs of Drosophila larvae carrying mutations in the abx, bx and pbx regulatory domains. In haltere discs, all five bx insertion mutations examined led to a general reduction in Ubx expression in the anterior compartment; for a given allele, the strength of the adult cuticle phenotype correlated with the degree of Ubx reduction. Deletions mapping near or overlapping the sites of bx insertions, including three abx alleles and the bx34e-prv(bx-prv) allele, showed greatly reduced Ubx expression in parts of the anterior compartment of the haltere disc; however, anterior patches of strong Ubx expression often remained, in highly variable patterns. As expected, the pbx1 mutation led to reduced Ubx expression in the posterior compartment of the haltere disc; surprisingly, pbx1 also led to altered expression of the en protein near the compartment border in the central region of the disc. In the metathoracic leg, all the bx alleles caused extreme reduction in Ubx expression in the anterior regions, with no allele-specific differences. In contrast, abx and bx-prv alleles resulted in patchy anterior reductions in third leg discs. In the larval central nervous system, abx but not bx alleles affected Ubx expression; the bx-prv deletion gave a wild-type phenotype, but it could not fully complement abx mutations. In the posterior wing disc, the bx-prv allele, and to a much lesser extent the bx34e chromosome from which it arose, led to ectopic expression of Ubx. Unlike other grain-of-function mutations in the BX-C, this phenotype appeared to be partially recessive to wild type. Finally, we asked whether the ppx transformation, which results from early lack of Ubx+ function in the mesothorax and is seen in abx animals, is due to ectopic Scr expression. Some mesothoracic leg and wing discs from abx2 larvae displayed ectopic expression of Scr, which was variable in extent but always confined to the posterior compartment.

scholarly journals Long noncoding RNA FER1L4 promotes the malignant processes of papillary thyroid cancer by targeting the miR-612/ Cadherin 4 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Luyao Wu ◽  
Yu Ding ◽  
Houchao Tong ◽  
Xi Zhuang ◽  
Jingsheng Cai ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Noncoding Rna ◽  
Animal Experiments ◽  
Ectopic Expression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Papillary Thyroid ◽  
Loss Of Function ◽  
Functional Roles

Abstract Background Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in various cancers. However, the functional roles of most lncRNA in papillary thyroid cancer (PTC) are not detailly understood. This study aims to investigate the biological function and molecular mechanism of lncRNA Fer-1 like family member 4 (FER1L4) in PTC. Methods The expression of FER1L4 in PTC was determined via operating quantitative real-time PCR assays. Meanwhile, the clinical significance of FER1L4 in patients with PTC was described. The biological functions of FER1L4 on PTC cells were evaluated by gain and loss of function experiments. Moreover, animal experiments were performed to reveal the effect on tumor growth. Subcellular distribution of FER1L4 was determined by fluorescence in situ hybridization and subcellular localization assays. Luciferase reporter assay and RNA immunoprecipitation assay were applied to define the relationship between FER1L4, miR-612, and Cadherin 4 (CDH4). Results Upregulated expression of FER1L4 in PTC tissues was positively correlated with lymph node metastasis (P = 0.020), extrathyroidal extension (P = 0.013) and advanced TNM stages (P = 0.013). In addition, knockdown of FER1L4 suppressed PTC cell proliferation, migration, and invasion, whereas ectopic expression of FER1L4 inversely promoted these processes. Mechanistically, FER1L4 could competitively bind with miR-612 to prevent the degradation of its target gene CDH4. This condition was further confirmed in the rescue assays. Conclusions This study first demonstrates FER1L4 plays an oncogenic role in PTC via a FER1L4-miR-612-CDH4 axis and may provide new therapeutic and diagnostic targets for PTC.

scholarly journals Modified laparoscopic lateral suspension with a five-arm mesh in pelvic organ prolapse surgery

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Eren Akbaba ◽  
Burak Sezgin
Keyword(s):  
Pelvic Organ Prolapse ◽  
De Novo ◽  
Pelvic Organ ◽  
Laparoscopic Technique ◽  
Life Questionnaire ◽  
Advanced Stage ◽  
Posterior Compartment ◽  
Anterior Compartment ◽  
Mesh Graft ◽  
Laparoscopic Lateral Suspension

Abstract Background Laparoscopic lateral suspension (LLS) is a laparoscopic technique used to treat pelvic organ prolapse (POP) in apical and anterior compartment defect with the use of a synthetic T-shaped mesh graft. The posterior compartment is repaired using a second mesh or a procedure along with LLS, such as posterior colporrhaphy. The aim of this study was to evaluate the clinical results of LLS for POP using a five-arm mesh instead of a T-shaped mesh graft to repair the defect of the posterior compartment in addition to the apical and anterior compartments. Methods Data from 37 patients with a diagnosis of advanced-stage (≥ 3) POP undergoing LLS with the use of a five-arm mesh were retrospectively analysed. Pre-operative and post-operative examinations and, surgical outcomes were determined. The results of measurements and examinations, reoperation rates, erosion rates, lower urinary tract symptoms, and complications were analysed. The Prolapse Quality of Life Questionnaire (P-QOL) was also used. Results The median post-operative follow-up was 20 (13–34) months. There was a significant improvement in POP-Q scores in all treated compartments, with overall objective cure rates of 94.5% for the apical compartment, 86.4% for the anterior compartment, and 91.8% for the posterior compartment. The median operative time was 96 (76–112) minutes. The median length of hospitalization was 2 (1–3) days. A significant improvement in vaginal bulge, urinary urgency, incomplete voiding, urinary frequency, and constipation was observed after surgery. The sexuality among patients increased from 13 (35.1%) preoperatively to 22 (59.4%) post-operatively. De novo stress urinary incontinence developed in 7 (18.9%) patients. The P-QOL scores improved significantly after surgery. Conclusions In advanced-stage POP patients, the posterior compartment damage can also be repaired in LLS with the use of a single five-arm mesh without the need for an additional procedure, and the recurrence rate can be reduced.

scholarly journals Partitioning of N-Ethylmaleimide-Sensitive Fusion (NSF) Protein Function in Drosophila melanogaster: dNSF1 Is Required in the Nervous System, and dNSF2 Is Required in Mesoderm

Genetics ◽  
2001 ◽  
Vol 158 (1) ◽  
pp. 265-278
Author(s):  
Jessica A Golby ◽  
Leigh Anna Tolar ◽  
Leo Pallanck
Keyword(s):  
Nervous System ◽  
Protein Function ◽  
Ectopic Expression ◽  
Drosophila Genome ◽  
Loss Of Function ◽  
Stage Of Development ◽  
Expression Studies ◽  
Larval Nervous System ◽  
Constitutive Secretion ◽  
Temporal And Spatial

Abstract The N-ethylmaleimide-sensitive fusion protein (NSF) promotes the fusion of secretory vesicles with target membranes in both regulated and constitutive secretion. While it is thought that a single NSF may perform this function in many eukaryotes, previous work has shown that the Drosophila genome contains two distinct NSF genes, dNSF1 and dNSF2, raising the possibility that each plays a specific secretory role. To explore this possibility, we generated mutations in the dNSF2 gene and used these and novel dNSF1 loss-of-function mutations to analyze the temporal and spatial requirements and the degree of functional redundancy between dNSF1 and dNSF2. Results of this analysis indicate that dNSF1 function is required in the nervous system beginning at the adult stage of development and that dNSF2 function is required in mesoderm beginning at the first instar larval stage of development. Additional evidence suggests that dNSF1 and dNSF2 may play redundant roles during embryonic development and in the larval nervous system. Ectopic expression studies demonstrate that the dNSF1 and dNSF2 gene products can functionally substitute for one another. These results indicate that the Drosophila NSF proteins exhibit similar functional properties, but have evolved distinct tissue-specific roles.

scholarly journals CHOP and c-JUN up-regulate the mutant Z α1-antitrypsin, exacerbating its aggregation and liver proteotoxicity

2020 ◽  
Vol 295 (38) ◽  
pp. 13213-13223
Author(s):  
Sergio Attanasio ◽  
Rosa Ferriero ◽  
Gwladys Gernoux ◽  
Rossella De Cegli ◽  
Annamaria Carissimo ◽  
...  
Keyword(s):  
Liver Disease ◽  
Er Stress ◽  
Proteinase Inhibitors ◽  
Pediatric Population ◽  
Transcriptional Response ◽  
Luciferase Reporter ◽  
Mrna Levels ◽  
Primary Role ◽  
Loss Of Function ◽  
Human Livers

α1-Antitrypsin (AAT) encoded by the SERPINA1 gene is an acute-phase protein synthesized in the liver and secreted into the circulation. Its primary role is to protect lung tissue by inhibiting neutrophil elastase. The Z allele of SERPINA1 encodes a mutant AAT, named ATZ, that changes the protein structure and leads to its misfolding and polymerization, which cause endoplasmic reticulum (ER) stress and liver disease through a gain-of-function toxic mechanism. Hepatic retention of ATZ results in deficiency of one of the most important circulating proteinase inhibitors and predisposes to early-onset emphysema through a loss-of-function mechanism. The pathogenetic mechanisms underlying the liver disease are not completely understood. C/EBP-homologous protein (CHOP), a transcription factor induced by ER stress, was found among the most up-regulated genes in livers of PiZ mice that express ATZ and in human livers of patients homozygous for the Z allele. Compared with controls, juvenile PiZ/Chop−/− mice showed reduced hepatic ATZ and a transcriptional response indicative of decreased ER stress by RNA-Seq analysis. Livers of PiZ/Chop−/− mice also showed reduced SERPINA1 mRNA levels. By chromatin immunoprecipitations and luciferase reporter–based transfection assays, CHOP was found to up-regulate SERPINA1 cooperating with c-JUN, which was previously shown to up-regulate SERPINA1, thus aggravating hepatic accumulation of ATZ. Increased CHOP levels were detected in diseased livers of children homozygous for the Z allele. In summary, CHOP and c-JUN up-regulate SERPINA1 transcription and play an important role in hepatic disease by increasing the burden of proteotoxic ATZ, particularly in the pediatric population.

scholarly journals Crosstalk of CREB and Fos/Jun on a single cis-element: transcriptional repression of the steroidogenic acute regulatory protein gene

2007 ◽  
Vol 39 (4) ◽  
pp. 261-277 ◽  
Author(s):  
Pulak R Manna ◽  
Douglas M Stocco
Keyword(s):  
Transcriptional Repression ◽  
Protein Gene ◽  
Binding Protein ◽  
Regulatory Protein ◽  
Ectopic Expression ◽  
Fine Tuning ◽  
Creb Binding Protein ◽  
Loss Of Function ◽  
Cis Element ◽  
Steroidogenic Acute Regulatory

AbstractTranscriptional regulation of the steroidogenic acute regulatory (StAR) protein gene by cAMP-dependent mechanisms occurs in the absence of a consensus cAMP-response element (CRE; TGACGTCA) and is mediated by several sequence-specific transcription factors. We previously identified three CRE-like sites (within the −151/−1 bp cAMP-responsive region of the mouse StAR gene), of which the CRE2 site overlaps with an activator protein-1 (AP-1) motif (TGACTGA, designated as CRE2/AP-1) that can bind both CRE and AP-1 DNA-binding proteins. The present studies were aimed at exploring the functional crosstalk between CREB (CRE-binding protein) and cFos/cJun (AP-1 family members) on the CRE2/AP-1 element and its role in regulating transcription of the StAR gene. Using MA-10 mouse Leydig tumor cells, we demonstrate that the CRE and AP-1 families of proteins interact with the CRE2/AP-1 sequence. CREB, cFos, and cJun proteins were found to bind to the CRE2/AP-1 motif but not the CRE1 and CRE3 sites. Treatment with the cAMP analog (Bu)2cAMP augmented phosphorylation of CREB (Ser133), cFos (Thr325), and cJun (ser73). Chromatin immunoprecipitation studies revealed that the induction of CREB, cFos, and cJun by (Bu)2cAMP was correlated with protein–DNA interactions and recruitment of the coactivator CREB-binding protein (CBP) to the StAR promoter. EMSA studies employing CREB and cFos/cJun proteins demonstrated competition between these factors for binding to the CRE2/AP-1 motif. Transfection of cells containing the −151/−1 StAR reporter with CREB and cFos/cJun resulted in trans-repression of the StAR gene, an event tightly associated with CBP, demonstrating that both CREB and Fos/Jun compete with each other for binding with limited amounts of intracellular CBP. Overexpression of adenovirus E1A, which binds and inactivates CBP, markedly suppressed StAR gene expression. Ectopic expression of CBP eliminated the repression of the StAR gene by E1A and potentiated the activity of CREB and cFos/cJun on StAR promoter responsiveness. These findings identify molecular events involved in crosstalk between CREB and cFos/cJun, which confer both gain and loss of function on a single cis-element in fine-tuning of the regulatory events involved in transcription of the StAR gene.

Computed Tomogram Findings of Mucous Recirculation between the Natural and Accessory Ostia of the Maxillary Sinus

2002 ◽  
Vol 16 (5) ◽  
pp. 265-268 ◽  
Author(s):  
Seung-Kyu Chung ◽  
Do Yeon Cho ◽  
Hun Jong Dhong
Keyword(s):  
Maxillary Sinus ◽  
Ring Structure ◽  
Endoscopic Examination ◽  
Mucous Secretion ◽  
Middle Portion ◽  
Anterior Portion ◽  
Posterior Portion

Background The phenomenon of recirculation involves the circulation of mucous secretion between the natural ostium and other openings and is observed mainly after surgery when the surgical opening is not connected. Methods Seven patients with a mucous stream transporting into an accessory ostium, as found during endoscopic examination, were entered into study. The coronal computed tomogram findings of the mucous recirculation were analyzed at three levels: anterior, middle, and posterior portion of it. Results The anterior portion was visualized at the level of the natural ostium in five patients. The middle portion inside the maxillary sinus was visible in six cases. The posterior portion was visualized at the level of the accessory ostium in five patients. Among the axial scans, mucous rings were visible in two patients. Conclusions The primary mucous recirculation between the natural and accessory openings is shown as a ring structure in coronal computed tomogram scans.

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