Control of tracheal tubulogenesis by Wingless signaling

Development ◽  
2000 ◽  
Vol 127 (20) ◽  
pp. 4433-4442 ◽  
Author(s):  
T. Chihara ◽  
S. Hayashi
Keyword(s):  
Tubular Epithelium ◽  
Signal Transducer ◽  
Tracheal System ◽  
Multiple Functions ◽  
Directed Migration ◽  
Tracheal Cell ◽  
Wingless Signaling ◽  
Unique Identity ◽  
Intracellular Signal

The tubular epithelium of the Drosophila tracheal system forms a network with a stereotyped pattern consisting of cells and branches with distinct identity. The tracheal primordium undergoes primary branching induced by the FGF homolog Branchless, differentiates cells with specialized functions such as fusion cells, which perform target recognition and adhesion during branch fusion, and extends branches toward specific targets. Specification of a unique identity for each primary branch is essential for directed migration, as a defect in either the EGFR or the Dpp pathway leads to a loss of branch identity and the misguidance of tracheal cell migration. Here, we investigate the role of Wingless signaling in the specification of cell and branch identity in the tracheal system. Wingless and its intracellular signal transducer, Armadillo, have multiple functions, including specifying the dorsal trunk through activation of Spalt expression and inducing differentiation of fusion cells in all fusion branches. Moreover, we show that Wingless signaling regulates Notch signaling by stimulating delta expression at the tip of primary branches. These activities of Wingless signaling together specify the shape of the dorsal trunk and other fusion branches.

ventral veinless, a POU domain transcription factor, regulates different transduction pathways required for tracheal branching in Drosophila

Development ◽  
1997 ◽  
Vol 124 (17) ◽  
pp. 3273-3281 ◽  
Author(s):  
M. Llimargas ◽  
J. Casanova
Keyword(s):  
Cell Migration ◽  
Target Genes ◽  
Branching Pattern ◽  
Specific Expression ◽  
Tracheal System ◽  
Tracheal Cell ◽  
Pou Domain ◽  
Tracheal Branching ◽  
Multicellular Organisms

Cell migration is an important step in a variety of developmental processes in many multicellular organisms. A particularly appropriate model to address the study of cell migration is the tracheal system of Drosophila, whose formation occurs by migration and fusion from clusters of ectodermal cells specified in each side of ten embryonic segments. Morphogenesis of the tracheal tree requires the activity of many genes, among them breathless (btl) and ventral veinless (vvl) whose mutations abolish tracheal cell migration. Activation of the btl receptor by branchless (bnl), its putative ligand, exerts an instructive role in the process of guiding tracheal cell migration. vvl has been shown to be required for the maintenance of btl expression during tracheal tree formation. Here we show that, in addition, vvl is independently required for the specific expression in the tracheal cells of thick veins (tkv) and rhomboid (rho), two genes whose mutations disrupt only particular branches of the tracheal system. Indeed, we show that expression in the tracheal cells of an activated form of tkv, the putative decapentaplegic (dpp) receptor, is able to induce shifts in their migration, asserting the role of the dpp pathway in establishing the branching pattern of the tracheal tree. In addition, by ubiquitous expression of the btl and tkv genes in vvl mutant embryos we show that both genes contribute to vvl function. These results indicate that through activation of its target genes, vvl makes the tracheal cells competent to further signalling and suggest that the btl transduction pathway could collaborate with other transduction pathways also regulated by vvl to specify the tracheal branching pattern.

Hedgehog signaling patterns the tracheal branches

Development ◽  
2001 ◽  
Vol 128 (9) ◽  
pp. 1599-1606 ◽  
Author(s):  
L. Glazer ◽  
B.Z. Shilo
Keyword(s):  
Cell Migration ◽  
Hedgehog Signaling ◽  
Egf Receptor ◽  
Cell Types ◽  
Fixed Number ◽  
Branching Pattern ◽  
Tracheal System ◽  
Tracheal Cell ◽  
Distinct Cell

The elaborate branching pattern of the Drosophila tracheal system originates from ten tracheal placodes on both sides of the embryo, each consisting of about 80 cells. Simultaneous cell migration from each tracheal pit in six different directions gives rise to the stereotyped branching pattern. Each branch contains a fixed number of cells. Previous work has shown that in the dorsoventral axis, localized activation of the Dpp, Wnt and EGF receptor (DER) pathways, subdivides the tracheal pit into distinct domains. We present the role of the Hedgehog (Hh) signaling system in patterning the tracheal branches. Hh is expressed in segmental stripes abutting the anterior border of the tracheal placodes. Induction of patched expression, which results from activation by Hh, demonstrates that cells in the anterior half of the tracheal pit are activated. In hh-mutant embryos migration of all tracheal branches is absent or stalled. These defects arise from a direct effect of Hh on tracheal cells, rather than by indirect effects on patterning of the ectoderm. Tracheal cell migration could be rescued by expressing Hh only in the tracheal cells, without rescuing the ectodermal defects. Signaling by several pathways, including the Hh pathway, thus serves to subdivide the uniform population of tracheal cells into distinct cell types that will subsequently be recruited into the different branches.

scholarly journals Dual function of the region-specific homeotic gene spalt during Drosophila tracheal system development

Development ◽  
1996 ◽  
Vol 122 (7) ◽  
pp. 2215-2223 ◽  
Author(s):  
R.P. Kuhnlein ◽  
R. Schuh
Keyword(s):  
Cell Migration ◽  
System Development ◽  
Dual Function ◽  
Homeotic Gene ◽  
Tracheal System ◽  
Directed Migration ◽  
Tracheal Cell ◽  
Distinct Subset ◽  
Directed Cell Migration ◽  
Placode Formation

We report that the region-specific homeotic gene spalt affects the Drosophila tracheal system at two different stages of embryonic development. Both lack-of-function and gain-of-function experiments show that blastodermal spalt activity restricts tracheal development to 10 bilaterally positioned pairs of tracheal placodes in the trunk region by repressing placode formation in parasegments 2, 3 and 14. The results suggest that the activity of the zinc-finger type transcription factor encoded by spalt suppresses the molecular pathway that establishes tracheal development. spalt function is also necessary for the directed migration of the dorsal trunk cells, a distinct subset of tracheal cells. This process is a prerequisite for the formation of the dorsal trunk generated by fusion of adjacent tracheal metameres into a common tubular structure. The directed cell migration, in which spalt gene function participates, seems to be independent of branch fusion and general tracheal cell migration processes.

scholarly journals Genetic Suppressor Element 1 (GSE1) Promotes the Oncogenic and Recurrent Phenotypes of Castration-Resistant Prostate Cancer by Targeting Tumor-Associated Calcium Signal Transducer 2 (TACSTD2)

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3959
Author(s):  
Oluwaseun Adebayo Bamodu ◽  
Yuan-Hung Wang ◽  
Chen-Hsun Ho ◽  
Su-Wei Hu ◽  
Chia-Da Lin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Disease Progression ◽  
Therapy Resistance ◽  
Calcium Signal ◽  
Signal Transducer ◽  
Castration Resistance ◽  
Castration Resistant

Background: prostate cancer (PCa) is a principal cause of cancer-related morbidity and mortality. Castration resistance and metastasis are clinical challenges and continue to impede therapeutic success, despite diagnostic and therapeutic advances. There are reports of the oncogenic activity of genetic suppressor element (GSE)1 in breast and gastric cancers; however, its role in therapy resistance, metastasis, and susceptibility to disease recurrence in PCa patients remains unclear. Objective: this study investigated the role of aberrantly expressed GSE1 in the metastasis, therapy resistance, relapse, and poor prognosis of advanced PCa. Methods: we used a large cohort of multi-omics data and in vitro, ex vivo, and in vivo assays to investigate the potential effect of altered GSE1 expression on advanced/castration-resistant PCa (CRPC) treatment responses, disease progression, and prognosis. Results: using a multi-cohort approach, we showed that GSE1 is upregulated in PCa, while tumor-associated calcium signal transducer 2 (TACSTD2) is downregulated. Moreover, the direct, but inverse, correlation interaction between GSE1 and TACSTD2 drives metastatic disease, castration resistance, and disease progression and modulates the clinical and immune statuses of patients with PCa. Patients with GSE1highTACSTD2low expression are more prone to recurrence and disease-specific death than their GSE1lowTACSTD2high counterparts. Interestingly, we found that the GSE1–TACSTD2 expression profile is associated with the therapy responses and clinical outcomes in patients with PCa, especially those with metastatic/recurrent disease. Furthermore, we demonstrate that the shRNA-mediated targeting of GSE1 (shGSE1) significantly inhibits cell proliferation and attenuates cell migration and tumorsphere formation in metastatic PC3 and DU145 cell lines, with an associated suppression of VIM, SNAI2, and BCL2 and the concomitant upregulation of TACSTD2 and BAX. Moreover, shGSE1 enhances sensitivity to the antiandrogens abiraterone and enzalutamide in vitro and in vivo. Conclusion: these data provide preclinical evidence of the oncogenic role of dysregulated GSE1–TACSTD2 signaling and show that the molecular or pharmacological targeting of GSE1 is a workable therapeutic strategy for inhibiting androgen-driven oncogenic signals, re-sensitizing CRPC to treatment, and repressing the metastatic/recurrent phenotypes of patients with PCa.

scholarly journals The Multifaced Role of STAT3 in Cancer and Its Implication for Anticancer Therapy

2021 ◽  
Vol 22 (2) ◽  
pp. 603
Author(s):  
Manlio Tolomeo ◽  
Antonio Cascio
Keyword(s):  
Tumor Promoter ◽  
Tumor Type ◽  
Signal Transducer ◽  
Suppressor Factor ◽  
Specific Tumor ◽  
Cytokine Stimulation ◽  
Pleiotropic Functions ◽  
Stat3 Mutations ◽  
Potent Tumor

Signal transducer and activator of transcription (STAT) 3 is one of the most complex regulators of transcription. Constitutive activation of STAT3 has been reported in many types of tumors and depends on mechanisms such as hyperactivation of receptors for pro-oncogenic cytokines and growth factors, loss of negative regulation, and excessive cytokine stimulation. In contrast, somatic STAT3 mutations are less frequent in cancer. Several oncogenic targets of STAT3 have been recently identified such as c-myc, c-Jun, PLK-1, Pim1/2, Bcl-2, VEGF, bFGF, and Cten, and inhibitors of STAT3 have been developed for cancer prevention and treatment. However, despite the oncogenic role of STAT3 having been widely demonstrated, an increasing amount of data indicate that STAT3 functions are multifaced and not easy to classify. In fact, the specific cellular role of STAT3 seems to be determined by the integration of multiple signals, by the oncogenic environment, and by the alternative splicing into two distinct isoforms, STAT3α and STAT3β. On the basis of these different conditions, STAT3 can act both as a potent tumor promoter or tumor suppressor factor. This implies that the therapies based on STAT3 modulators should be performed considering the pleiotropic functions of this transcription factor and tailored to the specific tumor type.

Pressure cycles and the water economy of insects

1988 ◽  
Vol 318 (1190) ◽  
pp. 377-407 ◽  
Keyword(s):  
Body Temperature ◽  
Water Exchange ◽  
Vapour Phase ◽  
The Body ◽  
Tracheal System ◽  
Water Economy ◽  
Insect Wings ◽  
Pressure Cycle ◽  
Respiratory Gases

Water exchange between insects and their environment via the vapour phase includes influx and efflux components. The pressure cycle theory postulates that insects (and some other arthropods) can regulate the relative rates of influx and efflux of water vapour by modulating hydrostatic pressures at a vapour-liquid interface by compressing or expanding a sealed, gas-filled cavity. Some such cavities, like the tracheal system, could be compressed by elevated pressure in all or part of the haemocoele. Others, perhaps including the muscular rectum of flea prepupae, could be compressed by intrinsic muscles. Maddrell Insect Physiol . 8, 199 (1971)) suggested a pressure cycle mechanism of this kind to account for rectal uptake of water vapour in Thermobia but did not find it compatible with quantitative information then available. Newer evidence conforms better with the proposed mechanism. Cyclical pressure changes are of widespread occurrence in insects and have sometimes been shown to depend on water status. Evidence is reviewed for the role of the tracheal system as an avenue for net exchange of water between the insect and its environment. Because water and respiratory gases share common pathways, most published findings fail to distinguish between the conventional view that the tracheal system has evolved as a site for distribution and exchange of respiratory gases and that any water exchange occurring in it is generally incidental and nonadaptive, and the theory proposed here. The pressure cycle theory offers a supplementary explanation not incompatible with evidence so far available. The relative importance of water economy and respiratory exchange in the functioning of compressible cavities such as the tracheal system remains to be explored. Some further implications of the pressure cycle theory are discussed. Consideration is given to the possible involvement of vapour-phase transport in the internal redistribution of water within the body. It is suggested that some insect wings may constitute internal vapour-liquid exchange sites, where water can move from the body fluids to the intratracheal gas. Ambient and body temperature must influence rates of vapour-liquid mass transfer. If elevated body temperature promotes evaporative discharge of the metabolic water burden that has been shown to accumulate during flight in some large insects, their minimum threshold thoracic temperature for sustained flight may relate to the maintenance of water balance. The role of water economy in the early evolution of insect wings is considered. Pressure cycles might help to maintain water balance in surface-breathing insects living in fresh and saline waters, but the turbulence of the surface of the open sea might prevent truly marine forms from using this mechanism.

The Role of Signal Transducer and Activator of Transcription 3 (Stat3) in Stretch Injury to Bladder Smooth Muscle Cells

2007 ◽  
Vol 3 ◽  
pp. S35
Author(s):  
Sarel Halachmi ◽  
Karen Aitken ◽  
Martha Szybowska ◽  
Nesrin Sabha ◽  
Shariff Dessouki ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Signal Transducer ◽  
Bladder Smooth Muscle ◽  
Stretch Injury ◽  
Transcription 3

scholarly journals Genetic Evidence for an Essential Role of Neuronally Expressed IL-6 Signal Transducer gp130 in the Induction and Maintenance of Experimentally Induced Mechanical Hypersensitivityin vivoandin vitro

2011 ◽  
Vol 7 ◽  
pp. 1744-8069-7-73 ◽  
Author(s):  
Serena Quarta ◽  
Christian Vogl ◽  
Cristina E Constantin ◽  
Nurcan Üçeyler ◽  
Claudia Sommer ◽  
...  
Keyword(s):  
Essential Role ◽  
Genetic Evidence ◽  
Signal Transducer ◽  
Experimentally Induced

Uterine epithelial LIF receptors contribute to implantation chamber formation in blastocyst attachment

Endocrinology ◽  
2021 ◽  
Author(s):  
Yamato Fukui ◽  
Yasushi Hirota ◽  
Tomoko Saito-Fujita ◽  
Shizu Aikawa ◽  
Takehiro Hiraoka ◽  
...  
Keyword(s):  
Hormone Receptor ◽  
Leukemia Inhibitory Factor ◽  
Ovarian Hormones ◽  
Signal Transducer ◽  
Blastocyst Implantation ◽  
Implantation Process ◽  
Uterine Glands ◽  
Transcription 3

Abstract Recent studies have demonstrated that the formation of an implantation chamber composed of a uterine crypt, an implantation-competent blastocyst, and uterine glands is a critical step in blastocyst implantation in mice. Leukemia inhibitory factor (LIF) activates signal transducer and activator of transcription 3 (STAT3) precursors via uterine LIF receptors (LIFRs), allowing successful blastocyst implantation. Our recent study revealed that the role of epithelial STAT3 is different from that of stromal STAT3. However, both are essential for blastocyst attachment, suggesting the different roles of epithelial and stromal LIFR in blastocyst implantation. However, how epithelial and stromal LIFR regulate the blastocyst implantation process remains unclear. To investigate the roles of LIFR in the uterine epithelium and stroma, we generated Lifr-floxed/lactoferrin (Ltf)-iCre (Lifr eKO) and Lifr-floxed/anti-Mullerian hormone receptor type 2 (Amhr2)-Cre (Lifr sKO) mice with deleted epithelial and stromal LIFR, respectively. Surprisingly, fertility and blastocyst implantation in the Lifr sKO mice were normal despite stromal STAT3 inactivation. In contrast, blastocyst attachment failed, and no implantation chambers were formed in the Lifr eKO mice with epithelial inactivation of STAT3. In addition, normal responsiveness to ovarian hormones was observed in the peri-implantation uteri of the Lifr eKO mice. These results indicate that the epithelial LIFR-STAT3 pathway initiates the formation of implantation chambers, leading to complete blastocyst attachment, and that stromal STAT3 regulates blastocyst attachment without stromal LIFR control. Thus, uterine epithelial LIFR is critical to implantation chamber formation and blastocyst attachment.

scholarly journals THE ORGANIZATION AND INNERVATION OF THE LUMINESCENT ORGAN IN A FIREFLY, PHOTURIS PENNSYLVANICA (COLEOPTERA)

1963 ◽  
Vol 16 (2) ◽  
pp. 323-359 ◽  
Author(s):  
David S. Smith
Keyword(s):  
Electron Microscope ◽  
Synaptic Vesicles ◽  
Light Emission ◽  
Nerve Endings ◽  
Tracheal Epithelium ◽  
Nerve Terminals ◽  
Tracheal System ◽  
Physiological Evidence ◽  
Effector System

The organization of the luminescent organ of an adult firefly has been studied with the electron microscope, and particular attention has been given to the disposition of nerve terminals within the organ. The cytological structure of the cells of the tracheal system, the peripheral and terminal axons, the photocytes and the cells of the dorsal ("reflecting") layer is described. Previous observations on the peripheral course of nerve branches alongside the tracheal trunks at the level of the dorsal layer and photocyte epithelium have been confirmed, and specialised nerve endings containing axoplasmic components structurally identical with "synaptic vesicles" and "neurosecretory droplets" have been identified, not in association with the surface of the photocytes, but lying between the apposed surfaces of two components of the tracheal epithelium: the tracheal end-cell and the tracheolar cell. These cytological findings are discussed in terms of available biochemical and physiological evidence concerning the mechanism of light emission in the firefly, especially with respect to the possible role of chemical "transmitter" action in triggering a response in a luminescent effector system.

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