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.

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.

The Notch pathway helps to pattern the tips of the Drosophila tracheal branches by selecting cell fates

Development ◽  
1999 ◽  
Vol 126 (11) ◽  
pp. 2355-2364 ◽  
Author(s):  
M. Llimargas
Keyword(s):  
Notch Pathway ◽  
Cell Types ◽  
Notch Signalling ◽  
Branching Pattern ◽  
Cell Fates ◽  
Tracheal System ◽  
Notch Signalling Pathway ◽  
Tracheal Cell ◽  
Mutant Phenotypes ◽  
Selection Of

The Drosophila tracheal system consists of a stereotyped network of epithelial tubes formed by several tracheal cell types. By the end of embryogenesis, when the general branching pattern is established, some specialised tracheal cells then mediate branch fusion while others extend fine terminal branches. Here evidence is presented that the Notch signalling pathway acts directly in the tracheal cells to distinguish individual fates within groups of equivalent cells. Notch helps to single out those tracheal cells that mediate branch fusion by blocking their neighbours from adopting the same fate. This function of Notch would require the restricted activation of the pathway in specific cells. In addition, and probably later, Notch also acts in the selection of those tracheal cells that extend the terminal branches. Both the localised expression and the mutant phenotypes of Delta, a known ligand for Notch, suggest that Delta may activate Notch to specify cell fates at the tips of the developing tracheal branches.

ribbon encodes a novel BTB/POZ protein required for directed cell migration in Drosophila melanogaster

Development ◽  
2001 ◽  
Vol 128 (15) ◽  
pp. 3001-3015 ◽  
Author(s):  
Pamela L. Bradley ◽  
Deborah J. Andrew
Keyword(s):  
Cell Migration ◽  
Wnt Signaling ◽  
Signaling Pathways ◽  
Egf Receptor ◽  
Tracheal System ◽  
Directed Cell Migration ◽  
Posterior Migration ◽  
And Function ◽  
Dorsal Epidermis ◽  
Anterior Posterior

During development, directed cell migration is crucial for achieving proper shape and function of organs. One well-studied example is the embryonic development of the larval tracheal system of Drosophila, in which at least four signaling pathways coordinate cell migration to form an elaborate branched network essential for oxygen delivery throughout the larva. FGF signaling is required for guided migration of all tracheal branches, whereas the DPP, EGF receptor, and Wingless/WNT signaling pathways each mediate the formation of specific subsets of branches. Here, we characterize ribbon, which encodes a BTB/POZ-containing protein required for specific tracheal branch migration. In ribbon mutant tracheae, the dorsal trunk fails to form, and ventral branches are stunted; however, directed migrations of the dorsal and visceral branches are largely unaffected. The dorsal trunk also fails to form when FGF or Wingless/WNT signaling is lost, and we show that ribbon functions downstream of, or parallel to, these pathways to promote anterior-posterior migration. Directed cell migration of the salivary gland and dorsal epidermis are also affected in ribbon mutants, suggesting that conserved mechanisms may be employed to orient cell migrations in multiple tissues during development.

scholarly journals Intravital 2-photon imaging reveals distinct morphology and infiltrative properties of glioblastoma-associated macrophages

2019 ◽  
Vol 116 (28) ◽  
pp. 14254-14259 ◽  
Author(s):  
Zhihong Chen ◽  
James L. Ross ◽  
Dolores Hambardzumyan
Keyword(s):  
Cell Types ◽  
Lineage Tracing ◽  
Response To Therapy ◽  
Vascular Endothelial ◽  
Distinct Cell ◽  
Attractive Option ◽  
Endothelial Growth Factor ◽  
Distinct Morphology ◽  
Cx3cr1 Expression

Characterized by a dismal survival rate and limited response to therapy, glioblastoma (GBM) remains one of the most aggressive human malignancies. Recent studies of the role of tumor-associated macrophages (TAMs) in the progression of GBMs have demonstrated that TAMs are significant contributors to tumor growth, invasion, and therapeutic resistance. TAMs, which include brain-resident microglia and circulating bone marrow derived-monocytes (BMDMs), are typically grouped together in histopathological and molecular analyses due to the lack of reliable markers of distinction. To develop more effective therapies aimed at specific TAM populations, we must first understand how these cells differ both morphologically and behaviorally. Furthermore, we must develop a deeper understanding of the mechanisms encouraging their infiltration and how these mechanisms can be therapeutically exploited. In this study, we combined immunocompetent lineage tracing mouse models of GBM with high-resolution open-skull 2-photon microscopy to investigate the phenotypical and functional characteristics of TAMs. We demonstrate that TAMs are composed of 2 morphologically distinct cell types that have differential migratory propensities. We show that BMDMs are smaller, minimally branched cells that are highly migratory compared with microglia, which are larger, highly branched stationary cells. In addition, 2 populations of monocytic macrophages were observed that differed in terms of CX3CR1 expression and migratory capacity. Finally, we demonstrate the efficacy of anti-vascular endothelial growth factor A blockade for prohibiting TAM infiltration, especially against BMDMs. Taken together, our data clearly define characteristics of individual TAM populations and suggest that combination therapy with antivascular and antichemotaxis therapy may be an attractive option for treating these tumors.

scholarly journals Hedgehog signaling to distinct cell types differentially regulates coronary artery and vein development

Development ◽  
2008 ◽  
Vol 135 (18) ◽  
pp. 3161-3171 ◽  
Author(s):  
K. J. Lavine ◽  
F. Long ◽  
K. Choi ◽  
C. Smith ◽  
D. M. Ornitz
Keyword(s):  
Coronary Artery ◽  
Hedgehog Signaling ◽  
Cell Types ◽  
Distinct Cell

scholarly journals An Opaque Cell-Specific Expression Program of Secreted Proteases and Transporters Allows Cell-Type Cooperation in Candida albicans

Genetics ◽  
2020 ◽  
Vol 216 (2) ◽  
pp. 409-429
Author(s):  
Matthew B. Lohse ◽  
Lucas R. Brenes ◽  
Naomi Ziv ◽  
Michael B. Winter ◽  
Charles S. Craik ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Opportunistic Pathogen ◽  
Cell Types ◽  
Specific Expression ◽  
Environmental Signals ◽  
Single Genome ◽  
Distinct Cell ◽  
Secreted Proteases ◽  
Expression Program

An unusual feature of the opportunistic pathogen Candida albicans is its ability to switch stochastically between two distinct, heritable cell types called white and opaque. Here, we show that only opaque cells, in response to environmental signals, massively upregulate a specific group of secreted proteases and peptide transporters, allowing exceptionally efficient use of proteins as sources of nitrogen. We identify the specific proteases [members of the secreted aspartyl protease (SAP) family] needed for opaque cells to proliferate under these conditions, and we identify four transcriptional regulators of this specialized proteolysis and uptake program. We also show that, in mixed cultures, opaque cells enable white cells to also proliferate efficiently when proteins are the sole nitrogen source. Based on these observations, we suggest that one role of white-opaque switching is to create mixed populations where the different phenotypes derived from a single genome are shared between two distinct cell types.

Role of the EGFR/Ras/Raf pathway in specification of photoreceptor cells in the Drosophila retina

Development ◽  
2001 ◽  
Vol 128 (7) ◽  
pp. 1183-1191 ◽  
Author(s):  
L. Yang ◽  
N.E. Baker
Keyword(s):  
Map Kinase ◽  
Egf Receptor ◽  
Eye Development ◽  
Photoreceptor Cells ◽  
Cell Types ◽  
Cell Specification ◽  
Kinase Activation ◽  
Cell Spacing ◽  
Egfr Activation

The Drosophila EGF receptor is required for differentiation of many cell types during eye development. We have used mosaic analysis with definitive null mutations to analyze the effects of complete absence of EGFR, Ras or Raf proteins during eye development. The Egfr, ras and raf genes are each found to be essential for recruitment of R1-R7 cells. In addition Egfr is autonomously required for MAP kinase activation. EGFR is not essential for R8 cell specification, either alone or redundantly with any other receptor that acts through Ras or Raf, or by activating MAP kinase. As with Egfr, loss of ras or raf perturbs the spacing and arrangement of R8 precursor cells. R8 cell spacing is not affected by loss of argos in posteriorly juxtaposed cells, which rules out a model in which EGFR acts through argos expression to position R8 specification in register between adjacent columns of ommatidia. The R8 spacing role of the EGFR was partially affected by simultaneous deletion of spitz and vein, two ligand genes, but the data suggest that EGFR activation independent of spitz and vein is also involved. The results prove that R8 photoreceptors are specified and positioned by distinct mechanisms from photoreceptors R1-R7.

scholarly journals Kakapo, a Novel Cytoskeletal-associated Protein Is Essential for the Restricted Localization of the Neuregulin-like Factor, Vein, at the Muscle–Tendon Junction Site

1998 ◽  
Vol 143 (5) ◽  
pp. 1259-1270 ◽  
Author(s):  
Dan Strumpf ◽  
Talila Volk
Keyword(s):  
Cell Differentiation ◽  
Egf Receptor ◽  
Cell Types ◽  
Drosophila Embryo ◽  
Tendon Cell ◽  
Distinct Cell ◽  
Tendon Cells ◽  
Junction Site ◽  
Receptor Signaling Pathway ◽  
Correct Association

In the Drosophila embryo, the correct association of muscles with their specific tendon cells is achieved through reciprocal interactions between these two distinct cell types. Tendon cell differentiation is initiated by activation of the EGF-receptor signaling pathway within these cells by Vein, a neuregulin-like factor secreted by the approaching myotube. Here, we describe the cloning and the molecular and genetic analyses of kakapo, a Drosophila gene, expressed in the tendons, that is essential for muscle-dependent tendon cell differentiation. Kakapo is a large intracellular protein and contains structural domains also found in cytoskeletal-related vertebrate proteins (including plakin, dystrophin, and Gas2 family members). kakapo mutant embryos exhibit abnormal muscle-dependent tendon cell differentiation. A major defect in the kakapo mutant tendon cells is the failure of Vein to be localized at the muscle–tendon junctional site; instead, Vein is dispersed and its levels are reduced. This may lead to aberrant differentiation of tendon cells and consequently to the kakapo mutant deranged somatic muscle phenotype.

scholarly journals Human platelets exert cytotoxic effects on tumor cells

Blood ◽  
1985 ◽  
Vol 65 (5) ◽  
pp. 1252-1255 ◽  
Author(s):  
GM Ibele ◽  
NE Kay ◽  
GJ Johnson ◽  
HS Jacob
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Types ◽  
Human Platelets ◽  
Fixed Number ◽  
Cell Cytotoxicity ◽  
Lipoxygenase Inhibitor ◽  
Tumor Metastases

Abstract Monocytes are thought to play a role in host resistance to tumor cell growth in animals and humans. In addition, platelets are known to be involved in tumor metastases. To investigate the interaction of these two cell types and their effect on tumor cells, human monocytes and platelets were examined using an in vitro monocyte-tumor cell cytotoxicity assay. Monocytes alone resulted in 32% +/- 1.5 (mean +/- SEM) tumor cell kill. When platelets were added to monocytes in a 1:1 ratio, an increase in cytotoxicity to 61% +/- 3.2 was observed. The cytotoxicity noted when platelets were added to a fixed number of monocytes and tumor cells was dependent on the number of platelets added. A decrease in cytotoxicity from 32% +/- 1.5 to 12% +/- 2.3 was observed when contaminating platelets were removed from monocyte preparations. Platelets added to tumor cells in the absence of any monocytes were also toxic, resulting in a maximum kill of 95% at a 4:1 platelet/tumor cell ratio. Secreted products of freshly isolated platelets may be responsible for much of the observed cytotoxicity, since supernatants from the platelets were toxic for tumor cells. Platelets pretreated with a cyclooxygenase inhibitor (ASA) or a lipoxygenase inhibitor had decreased cytotoxicity compared with untreated platelets. Our results indicate that products of platelet arachidonate metabolism are toxic for tumor cell lines. They also suggest that the role of the platelet must be considered when studying monocyte-tumor cell cytotoxicity.

scholarly journals Mechanochemical feedback underlies coexistence of qualitatively distinct cell polarity patterns within diverse cell populations

2017 ◽  
Vol 114 (28) ◽  
pp. E5750-E5759 ◽  
Author(s):  
JinSeok Park ◽  
William R. Holmes ◽  
Sung Hoon Lee ◽  
Hong-Nam Kim ◽  
Deok-Ho Kim ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Cell Types ◽  
Small Gtpases ◽  
Cell Polarization ◽  
Environmental Perturbations ◽  
Oscillatory Dynamic ◽  
Distinct Cell ◽  
Spatially Distributed ◽  
Directional Cell Migration

Cell polarization and directional cell migration can display random, persistent, and oscillatory dynamic patterns. However, it is not clear whether these polarity patterns can be explained by the same underlying regulatory mechanism. Here, we show that random, persistent, and oscillatory migration accompanied by polarization can simultaneously occur in populations of melanoma cells derived from tumors with different degrees of aggressiveness. We demonstrate that all of these patterns and the probabilities of their occurrence are quantitatively accounted for by a simple mechanism involving a spatially distributed, mechanochemical feedback coupling the dynamically changing extracellular matrix (ECM)–cell contacts to the activation of signaling downstream of the Rho-family small GTPases. This mechanism is supported by a predictive mathematical model and extensive experimental validation, and can explain previously reported results for diverse cell types. In melanoma, this mechanism also accounts for the effects of genetic and environmental perturbations, including mutations linked to invasive cell spread. The resulting mechanistic understanding of cell polarity quantitatively captures the relationship between population variability and phenotypic plasticity, with the potential to account for a wide variety of cell migration states in diverse pathological and physiological conditions.

Sign in / Sign up

Export Citation Format

Share Document