scholarly journals Feedback regulation of cytoneme-mediated transport shapes a tissue-specific FGF morphogen gradient

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Lijuan Du ◽  
Alex Sohr ◽  
Ge Yan ◽  
Sougata Roy
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Imaginal Disc ◽  
Feedback Regulation ◽  
Wing Disc ◽  
Wing Imaginal Disc ◽  
Morphogen Gradient ◽  
Signaling Proteins ◽  
Tissue Specific ◽  
Gradient Formation

Gradients of signaling proteins are essential for inducing tissue morphogenesis. However, mechanisms of gradient formation remain controversial. Here we characterized the distribution of fluorescently-tagged signaling proteins, FGF and FGFR, expressed at physiological levels from the genomic knock-in alleles in Drosophila. FGF produced in the larval wing imaginal-disc moves to the air-sac-primordium (ASP) through FGFR-containing cytonemes that extend from the ASP to contact the wing-disc source. The number of FGF-receiving cytonemes extended by ASP cells decreases gradually with increasing distance from the source, generating a recipient-specific FGF gradient. Acting as a morphogen in the ASP, FGF activates concentration-dependent gene expression, inducing pointed-P1 at higher and cut at lower levels. The transcription-factors Pointed-P1 and Cut antagonize each other and differentially regulate formation of FGFR-containing cytonemes, creating regions with higher-to-lower numbers of FGF-receiving cytonemes. These results reveal a robust mechanism where morphogens self-generate precise tissue-specific gradient contours through feedback regulation of cytoneme-mediated dispersion.

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.

scholarly journals Regulated delivery controls Drosophila Hedgehog, Wingless and Decapentaplegic signaling

2020 ◽  
Author(s):  
Ryo Hatori ◽  
Thomas B. Kornberg
Keyword(s):  
Signal Transduction ◽  
Imaginal Disc ◽  
Wing Disc ◽  
Bone Morphogenic Protein ◽  
Wing Imaginal Disc ◽  
Target Cells ◽  
Signaling Proteins ◽  
Common Pool ◽  
Drosophila Wing ◽  
Disc Cells

AbstractMorphogen signaling proteins disperse across tissues to activate signal transduction in target cells. We investigated dispersion of Hedgehog (Hh), Wingless (Wg), and Bone morphogenic protein homolog Decapentaplegic (Dpp) in the Drosophila wing imaginal disc, and found that delivery to targets is regulated. Cells take up <5% Hh produced, and neither amounts taken up nor extent of signaling changes under conditions of Hh production from 50-200% normal amounts. Similarly, cells take up <25% Wg produced, and variation in Wg production from 50-700% normal has no effect on amounts taken up or signaling. Similar properties were observed for Dpp. Wing disc-produced Hh signals to disc-associated tracheal and myoblast as well as an approximately equal number of disc cells, but the extent of signaling in the disc is unaffected by the presence or absence of the tracheal cells and myoblasts. These findings show that target cells do not take up signaling proteins from a common pool and that both the amount and destination of delivered morphogens are regulated..SummaryThe extent of Hh, Wg, and Dpp signaling is independent of the amount of signal produced or the number of recipient cells.

scholarly journals Gastrointestinal transcription factors drive lineage-specific developmental programs in organ specification and cancer

2019 ◽  
Vol 5 (12) ◽  
pp. eaax8898 ◽  
Author(s):  
Roshane Francis ◽  
Haiyang Guo ◽  
Catherine Streutker ◽  
Musaddeque Ahmed ◽  
Theodora Yung ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Epigenetic Regulation ◽  
Gastrointestinal Cancer ◽  
Chromatin Accessibility ◽  
Lineage Specification ◽  
Developmental Programs ◽  
Tissue Specific ◽  
Cancer Data ◽  
Gastrointestinal Tissue

Transcription factors (TFs) are spatially and temporally regulated during gut organ specification. Although accumulating evidence shows aberrant reactivation of developmental programs in cancer, little is known about how TFs drive lineage specification in development and cancer. We first defined gastrointestinal tissue–specific chromatin accessibility and gene expression during development, identifying the dynamic epigenetic regulation of SOX family of TFs. We revealed that Sox2 is not only essential for gastric specification, by maintaining chromatin accessibility at forestomach lineage loci, but also sufficient to promote forestomach/esophageal transformation upon Cdx2 deletion. By comparing our gastrointestinal lineage-specific transcriptome to human gastrointestinal cancer data, we found that stomach and intestinal lineage-specific programs are reactivated in Sox2high/Sox9high and Cdx2high cancers, respectively. By analyzing mice deleted for both Sox2 and Sox9, we revealed their potentially redundant roles in both gastric development and cancer, highlighting the importance of developmental lineage programs reactivated by gastrointestinal TFs in cancer.

scholarly journals Three neighboring genes interact with the Broad-Complex and the Stubble-stubbloid locus to affect imaginal disc morphogenesis in Drosophila.

Genetics ◽  
1991 ◽  
Vol 127 (4) ◽  
pp. 747-759 ◽  
Author(s):  
P J Gotwals ◽  
J W Fristrom
Keyword(s):  
Drosophila Melanogaster ◽  
Transcription Factors ◽  
Genetic Markers ◽  
Imaginal Disc ◽  
Wing Disc ◽  
Unit Interval ◽  
Genetic Interactions ◽  
Wild Type ◽  
Recessive Lethal ◽  
Broad Complex

Abstract The Broad-Complex (BR-C) is a complex regulatory locus at 2B-5 on the X chromosome of Drosophila melanogaster. The wild-type BR-C products are apparent transcription factors necessary for imaginal disc morphogenesis. Alleles of the Stubble-stubbloid (Sb-sbd) locus at 89B9-10 act as dominant enhancers of broad alleles of the BR-C. Sb-sbd wild-type products are necessary for appendage elongation. We report, here, on three new loci implicated in imaginal disc morphogenesis based on their genetic interactions with both BR-C and/or Sb-sbd mutants. Enhancer of broad (E(br)) was identified as a dominant enhancer of the br1 allele of the BR-C and is a recessive lethal. Mapping of E(br) has led to the identification of two loci, blistered and l(2)B485, mutants of which interact with E(br) and the Sb-sbd locus. Blistered, but not l(2)B485, interacts strongly with the BR-C. Alleles of the blistered locus are viable and disrupt proper wing disc morphogenesis independent of genetic interactions. All three loci map within the 0.6-map unit interval between the genetic markers speck and Irregular facets and to the cytological region 60C5-6; 60E9-10 at the tip of chromosome 2R. Genetic evidence is consistent with the view that the BR-C regulates blistered.

scholarly journals The SUMO ligase Su(var)2-10 controls eu- and heterochromatic gene expression via establishment of H3K9 trimethylation and negative feedback regulation

2019 ◽  
Author(s):  
Maria Ninova ◽  
Baira Godneeva ◽  
Yung-Chia Ariel Chen ◽  
Yicheng Luo ◽  
Sharan J. Prakash ◽  
...  
Keyword(s):  
Gene Expression ◽  
Negative Feedback ◽  
Feedback Regulation ◽  
Specific Gene ◽  
Negative Feedback Regulation ◽  
Tissue Specific ◽  
Tissue Specific Gene ◽  
H3k9 Trimethylation ◽  
Sumo Ligase ◽  
Host Genes

AbstractChromatin is critical for genome compaction and gene expression. On a coarse scale, the genome is divided into euchromatin, which harbors the majority of genes and is enriched in active chromatin marks, and heterochromatin, which is gene-poor but repeat-rich. The conserved molecular hallmark of heterochromatin is the H3K9me3 modification, which is associated with gene silencing. We found that in Drosophila deposition of most of the H3K9me3 mark depends on SUMO and the SUMO-ligase Su(var)2-10, which recruits the histone methyltransferase complex SetDB1/Wde. In addition to repressing repeats, H3K9me3 also influences expression of both hetero- and euchromatic host genes. High H3K9me3 levels in heterochromatin are required to suppress spurious non-canonical transcription and ensure proper gene expression. In euchromatin, a set of conserved genes is repressed by Su(var)2-10/SetDB1-induced H3K9 trimethylation ensuring tissue-specific gene expression. Several components of heterochromatin are themselves repressed by this pathway providing a negative feedback mechanism to ensure chromatin homeostasis.Highlights-Proper expression of host genes residing in heterochromatin requires Su(var)2-10-dependent installation of the H3K9me3 mark to suppress spurious non-canonical transcription.-A set of euchromatic host genes is repressed by transposon-independent installation of H3K9me3 in a process that depends on Su(var)2-10 and SUMO.-Installation of H3K9me3 via Su(var)2-10 ensures tissue-specific gene expression.-H3K9me3-dependent silencing of genes encoding proteins involved in heterochromatin formation provides negative feedback regulation to maintain heterochromatin homeostasis.

scholarly journals Understanding the early cold response mechanism in IR64 indica rice variety through comparative transcriptome analysis

2020 ◽  
Author(s):  
Pratiti Dasgupta ◽  
Abhishek Das ◽  
Sambit Datta New ◽  
Ishani Banerjee New ◽  
Sucheta Tripathy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Low Temperature ◽  
Cold Stress ◽  
Cold Shock ◽  
Indica Rice ◽  
Cellular Reprogramming ◽  
Early Gene ◽  
Signaling Proteins ◽  
Cold Response

Abstract Background Cellular reprogramming in response to environmental stress involves alteration of gene expression, changes in the protein and metabolite profile for ensuring better stress management in plants. Similar to other plant species originating in tropical and sub-tropical areas, indica rice is highly sensitive to low temperature that adversely affects its growth and grain productivity. Substantial work has been done to understand cold induced changes in gene expression in rice plants. However, adequate information is not available for early gene expression, especially in indica variety. Therefore, a transcriptome profile was generated for cold shock treated seedlings of IR64 variety to identify early responsive genes. Results The functional annotation of early DEGs shows enrichment of genes involved in altered membrane rigidity and electrolytic leakage, the onset of calcium signaling, ROS generation and activation of stress responsive transcription factors in IR64. Gene regulatory network suggests that cold shock induces Ca 2+ signaling to activate DREB/CBF pathway and other groups of transcription factors such as MYB, NAC and ZFP; for activating various cold-responsive genes. The analysis also indicates that cold induced signaling proteins like RLKs, RLCKs, CDPKs and MAPKK and ROS signaling proteins. Further, several LEA, dehydrins and Low temperature-induced-genes were upregulated under early cold shock condition, indicating the onset of water-deficit conditions. Expression profiling in different high yielding cultivars shows high expression of cold-responsive genes in Heera and CB1 indica varieties, These varieties show low levels of cold induced ROS production, electrolytic leakage and high germination rate post-cold stress, compared to IR36 and IR64. Collectively, these results suggest that these varieties may have improved adaptability to cold stress. Conclusions The results of this study provide insights about early responsive events in Oryza sativa L.ssp. indica cv IR64 in response to cold stress. Our data shows the onset of cold response is associated with upregulation of stress responsive TFs, hydrophilic proteins and signaling molecules, whereas, the genes coding for cellular biosynthetic enzymes, cell cycle control and growth-related TFs are downregulated. This study reports that the generation of ROS is integral to the early response to trigger the ROS mediated signaling events during later stages.

Boundaries in the Drosophila wing imaginal disc organize vein-specific genetic programs

Development ◽  
1998 ◽  
Vol 125 (21) ◽  
pp. 4245-4257 ◽  
Author(s):  
B. Biehs ◽  
M.A. Sturtevant ◽  
E. Bier
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Short Range ◽  
Imaginal Disc ◽  
Larval Instar ◽  
Wing Imaginal Disc ◽  
Control Of Gene Expression ◽  
Present Evidence ◽  
The Third ◽  
Drosophila Wing

Previous studies have suggested that vein primordia in Drosophila form at boundaries along the A/P axis between discrete sectors of the larval wing imaginal disc. Genes involved in initiating vein development during the third larval instar are expressed either in narrow stripes corresponding to vein primordia or in broader ‘provein’ domains consisting of cells competent to become veins. In addition, genes specifying the alternative intervein cell fate are expressed in complementary intervein regions. The regulatory relationships between genes expressed in narrow vein primordia, in broad provein stripes and in interveins remains unknown, however. In this manuscript, we provide additional evidence for veins forming in narrow stripes at borders of A/P sectors. These experiments further suggest that narrow vein primordia produce secondary short-range signal(s), which activate expression of provein genes in a broad pattern in neighboring cells. We also show that crossregulatory interactions among genes expressed in veins, proveins and interveins contribute to establishing the vein-versus-intervein pattern, and that control of gene expression in vein and intervein regions must be considered on a stripe-by-stripe basis. Finally, we present evidence for a second set of vein-inducing boundaries lying between veins, which we refer to as paravein boundaries. We propose that veins develop at both vein and paravein boundaries in more ‘primitive’ insects, which have up to twice the number of veins present in Drosophila. We present a model in which different A/P boundaries organize vein-specific genetic programs to govern the development of individual veins.

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