-
Články
- Časopisy
- Kurzy
- Témy
- Kongresy
- Videa
- Podcasty
The Pathway Gene Functions together with the -Dependent Isoprenoid Biosynthetic Pathway to Orchestrate Germ Cell Migration
The Drosophila embryonic gonad is assembled from two distinct cell types, the Primordial Germ Cells (PGCs) and the Somatic Gonadal Precursor cells (SGPs). The PGCs form at the posterior of blastoderm stage embryos and are subsequently carried inside the embryo during gastrulation. To reach the SGPs, the PGCs must traverse the midgut wall and then migrate through the mesoderm. A combination of local repulsive cues and attractive signals emanating from the SGPs guide migration. We have investigated the role of the hedgehog (hh) pathway gene shifted (shf) in directing PGC migration. shf encodes a secreted protein that facilitates the long distance transmission of Hh through the proteoglycan matrix after it is released from basolateral membranes of Hh expressing cells in the wing imaginal disc. shf is expressed in the gonadal mesoderm, and loss - and gain-of-function experiments demonstrate that it is required for PGC migration. Previous studies have established that the hmgcr-dependent isoprenoid biosynthetic pathway plays a pivotal role in generating the PGC attractant both by the SGPs and by other tissues when hmgcr is ectopically expressed. We show that production of this PGC attractant depends upon shf as well as a second hh pathway gene gγ1. Further linking the PGC attractant to Hh, we present evidence indicating that ectopic expression of hmgcr in the nervous system promotes the release/transmission of the Hh ligand from these cells into and through the underlying mesodermal cell layer, where Hh can contact migrating PGCs. Finally, potentiation of Hh by hmgcr appears to depend upon cholesterol modification.
Vyšlo v časopise: The Pathway Gene Functions together with the -Dependent Isoprenoid Biosynthetic Pathway to Orchestrate Germ Cell Migration. PLoS Genet 9(9): e32767. doi:10.1371/journal.pgen.1003720
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003720Souhrn
The Drosophila embryonic gonad is assembled from two distinct cell types, the Primordial Germ Cells (PGCs) and the Somatic Gonadal Precursor cells (SGPs). The PGCs form at the posterior of blastoderm stage embryos and are subsequently carried inside the embryo during gastrulation. To reach the SGPs, the PGCs must traverse the midgut wall and then migrate through the mesoderm. A combination of local repulsive cues and attractive signals emanating from the SGPs guide migration. We have investigated the role of the hedgehog (hh) pathway gene shifted (shf) in directing PGC migration. shf encodes a secreted protein that facilitates the long distance transmission of Hh through the proteoglycan matrix after it is released from basolateral membranes of Hh expressing cells in the wing imaginal disc. shf is expressed in the gonadal mesoderm, and loss - and gain-of-function experiments demonstrate that it is required for PGC migration. Previous studies have established that the hmgcr-dependent isoprenoid biosynthetic pathway plays a pivotal role in generating the PGC attractant both by the SGPs and by other tissues when hmgcr is ectopically expressed. We show that production of this PGC attractant depends upon shf as well as a second hh pathway gene gγ1. Further linking the PGC attractant to Hh, we present evidence indicating that ectopic expression of hmgcr in the nervous system promotes the release/transmission of the Hh ligand from these cells into and through the underlying mesodermal cell layer, where Hh can contact migrating PGCs. Finally, potentiation of Hh by hmgcr appears to depend upon cholesterol modification.
Zdroje
1. HuangfuD, AndersonKV (2006) Signaling from Smo to Ci/Gli: conservation and divergence of Hedgehog pathways from Drosophila to vertebrates. Development 33 : 3–14.
2. MatiseM (2007) Order in the classroom: graded responses to instructive Hh signaling in the CNS. Cell Cycle 10 : 1194–9.
3. WilsonCW, ChuangPT (2010) Mechanism and evolution of cytosolic Hedgehog signal transduction. Development 137 : 2079–94.
4. MatiseMP, WangH (2011) Sonic hedgehog signaling in the developing CNS where it has been and where it is going. Curr Top Dev Biol 97 : 75–117.
5. TestazS, JarovA, WilliamsKP, LingLE, KotelianskyVE, et al. (2001) Sonic hedgehog restricts adhesion and migration of neural crest cells independently of the Patched-Smoothen-Gil signaling pathway. Proc Natl Acad Sci U S A 98 : 12521–12526.
6. HochmanE, CastielA, Jacob-HirschJ, AmariglioN, IzraeliS (2006) Molecular pathways regulating pro-migratory effects of Hedgehog signaling. J Biol Chem 281 33860–70.
7. CharronF, SteinE, JeongJ, McMahonAP, Tessier-LavigneM (2003) The morphogen sonic hedgehog is an axonal chemoattractant that collaborates with netrin-1 in midline axon guidance. Cell 113 : 11–23.
8. DeshpandeG, SwanhartL, ChiangP, SchedlP (2001) Hedgehog signaling in germ cell migration. Cell 106 : 759–69.
9. KatoK, ChiharaT, HayashiS (2004) Hedgehog and decapentabplegic instruct polarized growth of cell extensions in the Drosophila trachea. Development (Camb.) 131 : 5253–5261.
10. MannRK, BeachPA (2004) Novel lipid modifications of secreted protein signals. Annu Rev Biochem 2004 73 : 891–923.
11. GalletA (2011) Hedgehog morphogen: from secretion to reception. Trends Cell Biol 21 : 238–246.
12. GalletA, RodriguezR, Ruel L, TherondPP (2003) Cholesterol modification of hedgehog is required for trafficking and movement, revealing an asymmetric cellular response to hedgehog. Dev Cell 4 : 191–204.
13. AvanesovA, BlairSS (2013) The Drosophila WIF1 homolog Shifted maintainsglypican-independent Hedgehog signaling and interacts with the Hedgehog co-receptors Ihog and Boi. Development 140 : 107–16.
14. BilioniA, Sanchez-HernandezD, CallejoA, GradillaAC, IbanezC, et al. (2013) Balancing Hedgehog, a retention and release equilibrium given by Dally, Ihog, Boi and shifted/DmWif. Dev Biol 376 : 198–221.
15. CallejoA, TorrojaC, QuijadaL, GuerreroI (2006) Hedgehog lipid modifications are required for Hedgehog stabilization in the extracellular matrix. Development 133 : 471–83.
16. GalletA, RuelL, Staccini-LavenantL, ThérondPP (2006) Cholesterol modification is necessary for controlled planar long-range activity of Hedgehog in Drosophila epithelia. Development1 33 : 407–18.
17. TheI, BellaicheY, PerrimonN (1999) Hedgehog movement is regulated through tout velu-dependent synthesis of a heparan sulfate proteoglycan. Mol Cell 4 : 633–9.
18. HäckerU, NybakkenK, PerrimonN (2006) Heparan sulphate proteoglycans: the sweet side of development. Nat Rev Mol Cell Biol 6 : 530–41.
19. BurkeR, NellenD, BellottoM, HafenE, SentiKA, et al. (1999) Dispatched, a novel sterol-sensing domain protein dedicated to the release of cholesterol-modified hedgehog from signaling cells. Cell 99 : 803–15.
20. CallejoA, BilioniA, MollicaE, GorfinkielN, AndrésG, et al. (2011) Dispatched mediates Hedgehog basolateral release to form the long-range morphogenetic gradient in the Drosophila wing disk epithelium. Proc Natl Acad Sci U S A 108 : 12591–8.
21. DeshpandeG, SchedlP (2005) HMGCoA reductase potentiates hedgehog signaling in Drosophila melanogaster. Dev Cell 9 : 629–38.
22. DeshpandeG, GodishalaA, SchedlP (2009) Gγ1, a downstream target for the hmgcr-isoprenoid biosynthetic pathway, is required for releasing the Hedgehog ligand and directing germ cell migration. Plos Genetics 5 (1) e1000333 doi:10.1371/journal.pgen.1000333
23. DeBose-BoydRA (2008) Feedback regulation of cholesterol synthesis: sterol-accelerated ubiquitination and degradation of HMG CoA reductase. Cell Res 18 : 609–621.
24. SantosAC, LehmannR (2004) Isoprenoids control germ cell migration downstream of HMGCoA reductase. Dev Cell 6 : 283–93.
25. AnelAMD, MalhotraV (2005) PKCn is required for b1g2/b3g2 and PKD-mediated transport to the cell surface and the organization of the Golgi apparatus. Jour Cell Biol 169 : 83–91.
26. BardF, MalhotraV (2006) The formation of TGN to plasma membrane transport carriers. Annu Rev Cell Dev Biol 232 : 439–55.
27. Van DorenM, BroihierHT, MooreLA, LehmannR (1998) HMG-CoA reductase guides migrating primordial germ cells. Nature 396 : 466–9.
28. KunwarPS, SiekhausDE, LehmannR (2006) In vivo migration: A germ cell perspective. Annual Review of Cell. And Dev Biol 22 : 237–65.
29. RenaultAD, RicardoS, KunwarPS, SantosA, Starz-GaianoM, et al. (2009) Hedgehog does not guide migrating Drosophila germ cells. Dev Biol 328 : 355–62.
30. RichardsonBE, LehmannR (2010) Mechanisms guiding primordial germ cell migration: strategies from different organisms. Nat Rev Mol Cell Biol 11 : 37–49.
31. HsiehJC, KodjabachianL, RebbertML, RattnerA, SmallwoodPM, et al. (1999) A new secreted protein that binds to Wnt proteins and inhibits their activities. Nature 398 : 431–6.
32. GliseB, MillerCA, CrozatierM, HalbisenMA, WiseS, et al. (2005) Shifted, the Drosophila ortholog of Wnt inhibitory factor-1, controls the distribution and movement of Hedgehog. Dev Cell 8 : 255–66.
33. GorfinkielN, SierraJ, CallejoA, IbañezC, GuerreroI (2005) The Drosophila ortholog of the human Wnt inhibitor factor Shifted controls the diffusion of lipid-modified Hedgehog. Dev Cell 8 : 241–53.
34. AvanesovA, HoneyagerSM, MalickiJ, BlairSS (2012) The role of glypicans in Wnt inhibitory factor-1 activity and the structural basis of Wif1's effects on Wnt and Hedgehog signaling. PLoS Genet 8 (2) e1002503.
35. Callejo A, Culi J, Guerrero I (2007). Lipids and Lipoproteins as carriers for Hedgehog spreading and reception. Fly Meeting Abstracts. Drosophilia Research Conference. March 7–11, 2007. Philadelphia, Pennsylvania, United States of America.
36. DelonI, PayreF (2004) Evolution of larval morphology in flies: get in shape with shavenbaby. Trends Genet 20 : 305–13.
37. ZhaiZ, FuchsAL, LohmannI (2010) Cellular analysis of newly identified Hox downstream genes in Drosophila. Eur J Cell Biol 89 : 273–8.
38. RicardoS, LehmannR (2009) An ABC transporter controls export of a Drosophila germ cell attractant. Science 323 : 943–946.
39. TorrojaC, GorfinkielN, GuerreroI (2004) Patched controls the Hedgehog gradient by endocytosis in a dynamin-dependent manner, but this internalization does not play a major role in signal transduction. Development 131 : 2395–2408.
40. Sánchez-HernándezD, SierraJ, Ortigão-FariasJR, GuerreroI (2012) The WIF domain of the human and Drosophila Wif-1 secreted factors confers specificity for Wnt or Hedgehog. Development 2012 Sep 5. [Epub ahead of print].
41. BijlsmaMF, BorensztajnKS, RoelinkH, PeppelenboschMP, SpekCA (2007) Sonic hedgehog induces transcription-independent cytoskeletal rearrangement and migration regulated by arachidonate metabolites. Cell Signal 19 2596–604.
42. PolizioAH, ChinchillaP, ChenX, KimS, ManningDR, et al. (2011) Heterotrimeric Gi proteins link Hedgehog signaling to activation of Rho small GTPases to promote fibroblast migration. J Biol Chem 286 : 19589–96.
43. YiP, HanZ, LiX, OlsonEN (2006) The mevalonate pathway controls heart formation in Drosophila by isoprenylation of Ggamma1. Science 313 : 301–3.
Štítky
Genetika Reprodukčná medicína
Článek Rapid Intrahost Evolution of Human Cytomegalovirus Is Shaped by Demography and Positive SelectionČlánek Common Variants in Left/Right Asymmetry Genes and Pathways Are Associated with Relative Hand SkillČlánek Manipulating or Superseding Host Recombination Functions: A Dilemma That Shapes Phage EvolvabilityČlánek Maternal Depletion of Piwi, a Component of the RNAi System, Impacts Heterochromatin Formation inČlánek Hsp104 Suppresses Polyglutamine-Induced Degeneration Post Onset in a Drosophila MJD/SCA3 ModelČlánek Cooperative Interaction between Phosphorylation Sites on PERIOD Maintains Circadian Period inČlánek VAPB/ALS8 MSP Ligands Regulate Striated Muscle Energy Metabolism Critical for Adult Survival inČlánek Histone Chaperone NAP1 Mediates Sister Chromatid Resolution by Counteracting Protein Phosphatase 2AČlánek A Link between ORC-Origin Binding Mechanisms and Origin Activation Time Revealed in Budding YeastČlánek Genotype-Environment Interactions Reveal Causal Pathways That Mediate Genetic Effects on PhenotypeČlánek Chromatin-Specific Regulation of Mammalian rDNA Transcription by Clustered TTF-I Binding SitesČlánek Meiotic Recombination in Arabidopsis Is Catalysed by DMC1, with RAD51 Playing a Supporting Role
Článok vyšiel v časopisePLOS Genetics
Najčítanejšie tento týždeň
2013 Číslo 9- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
-
Všetky články tohto čísla
- The Pathway Gene Functions together with the -Dependent Isoprenoid Biosynthetic Pathway to Orchestrate Germ Cell Migration
- Take Off, Landing, and Fly Anesthesia
- Nucleosome Assembly Proteins Get SET to Defeat the Guardian of Chromosome Cohesion
- Whole-Exome Sequencing Reveals a Rapid Change in the Frequency of Rare Functional Variants in a Founding Population of Humans
- Evidence Is Evidence: An Interview with Mary-Claire King
- Rapid Intrahost Evolution of Human Cytomegalovirus Is Shaped by Demography and Positive Selection
- Convergent Transcription Induces Dynamic DNA Methylation at Loci
- Environmental Stresses Disrupt Telomere Length Homeostasis
- Ultra-Sensitive Sequencing Reveals an Age-Related Increase in Somatic Mitochondrial Mutations That Are Inconsistent with Oxidative Damage
- Common Variants in Left/Right Asymmetry Genes and Pathways Are Associated with Relative Hand Skill
- Genetic and Anatomical Basis of the Barrier Separating Wakefulness and Anesthetic-Induced Unresponsiveness
- The Locus, Exclusive to the Ambulacrarians, Encodes a Chromatin Insulator Binding Protein in the Sea Urchin Embryo
- Binding of NF-κB to Nucleosomes: Effect of Translational Positioning, Nucleosome Remodeling and Linker Histone H1
- Manipulating or Superseding Host Recombination Functions: A Dilemma That Shapes Phage Evolvability
- Dynamics of DNA Methylation in Recent Human and Great Ape Evolution
- Functional Dissection of Regulatory Models Using Gene Expression Data of Deletion Mutants
- PAQR-2 Regulates Fatty Acid Desaturation during Cold Adaptation in
- N-alpha-terminal Acetylation of Histone H4 Regulates Arginine Methylation and Ribosomal DNA Silencing
- A Genome-Wide Systematic Analysis Reveals Different and Predictive Proliferation Expression Signatures of Cancerous vs. Non-Cancerous Cells
- Maternal Depletion of Piwi, a Component of the RNAi System, Impacts Heterochromatin Formation in
- miR-1/133a Clusters Cooperatively Specify the Cardiomyogenic Lineage by Adjustment of Myocardin Levels during Embryonic Heart Development
- Hsp104 Suppresses Polyglutamine-Induced Degeneration Post Onset in a Drosophila MJD/SCA3 Model
- Genome-Wide Analysis of Genes and Their Association with Natural Variation in Drought Tolerance at Seedling Stage of L
- Deep Resequencing of GWAS Loci Identifies Rare Variants in , and That Are Associated with Ulcerative Colitis
- Cooperative Interaction between Phosphorylation Sites on PERIOD Maintains Circadian Period in
- VAPB/ALS8 MSP Ligands Regulate Striated Muscle Energy Metabolism Critical for Adult Survival in
- Analysis of Genes Reveals Redundant and Independent Functions in the Inner Ear
- Predicting the Risk of Rheumatoid Arthritis and Its Age of Onset through Modelling Genetic Risk Variants with Smoking
- Histone Chaperone NAP1 Mediates Sister Chromatid Resolution by Counteracting Protein Phosphatase 2A
- A Shift to Organismal Stress Resistance in Programmed Cell Death Mutants
- Fragile Site Instability in Causes Loss of Heterozygosity by Mitotic Crossovers and Break-Induced Replication
- Tracking of Chromosome and Replisome Dynamics in Reveals a Novel Chromosome Arrangement
- The Condition-Dependent Transcriptional Landscape of
- Ago1 Interacts with RNA Polymerase II and Binds to the Promoters of Actively Transcribed Genes in Human Cancer Cells
- Nebula/DSCR1 Upregulation Delays Neurodegeneration and Protects against APP-Induced Axonal Transport Defects by Restoring Calcineurin and GSK-3β Signaling
- System-Wide Analysis Reveals a Complex Network of Tumor-Fibroblast Interactions Involved in Tumorigenicity
- Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations
- and Are Required for Cellularization and Differentiation during Female Gametogenesis in
- Growth factor independent-1 Maintains Notch1-Dependent Transcriptional Programming of Lymphoid Precursors
- Whole Genome Sequencing Identifies a Deletion in Protein Phosphatase 2A That Affects Its Stability and Localization in
- An Alteration in ELMOD3, an Arl2 GTPase-Activating Protein, Is Associated with Hearing Impairment in Humans
- Genomic Identification of Founding Haplotypes Reveals the History of the Selfing Species
- Plasticity Regulators Modulate Specific Root Traits in Discrete Nitrogen Environments
- The IDD14, IDD15, and IDD16 Cooperatively Regulate Lateral Organ Morphogenesis and Gravitropism by Promoting Auxin Biosynthesis and Transport
- Stochastic Loss of Silencing of the Imprinted Allele, in a Mouse Model and Humans with Prader-Willi Syndrome, Has Functional Consequences
- The Prefoldin Complex Regulates Chromatin Dynamics during Transcription Elongation
- PKA Controls Calcium Influx into Motor Neurons during a Rhythmic Behavior
- A Pre-mRNA-Splicing Factor Is Required for RNA-Directed DNA Methylation in
- Cell-Type Specific Features of Circular RNA Expression
- The Uve1 Endonuclease Is Regulated by the White Collar Complex to Protect from UV Damage
- An Atypical Kinase under Balancing Selection Confers Broad-Spectrum Disease Resistance in Arabidopsis
- Genome-Wide Mutation Avalanches Induced in Diploid Yeast Cells by a Base Analog or an APOBEC Deaminase
- Extensive Divergence of Transcription Factor Binding in Embryos with Highly Conserved Gene Expression
- Bi-modal Distribution of the Second Messenger c-di-GMP Controls Cell Fate and Asymmetry during the Cell Cycle
- Cell Interactions and Patterned Intercalations Shape and Link Epithelial Tubes in
- A Link between ORC-Origin Binding Mechanisms and Origin Activation Time Revealed in Budding Yeast
- The Genome and Development-Dependent Transcriptomes of : A Window into Fungal Evolution
- SKN-1/Nrf, A New Unfolded Protein Response Factor?
- The Highly Prolific Phenotype of Lacaune Sheep Is Associated with an Ectopic Expression of the Gene within the Ovary
- Fusion of Large-Scale Genomic Knowledge and Frequency Data Computationally Prioritizes Variants in Epilepsy
- IL-17 Attenuates Degradation of ARE-mRNAs by Changing the Cooperation between AU-Binding Proteins and microRNA16
- An Enhancer Element Harboring Variants Associated with Systemic Lupus Erythematosus Engages the Promoter to Influence A20 Expression
- Genome Analysis of a Transmissible Lineage of Reveals Pathoadaptive Mutations and Distinct Evolutionary Paths of Hypermutators
- Type I-E CRISPR-Cas Systems Discriminate Target from Non-Target DNA through Base Pairing-Independent PAM Recognition
- Divergent Transcriptional Regulatory Logic at the Intersection of Tissue Growth and Developmental Patterning
- MEIOB Targets Single-Strand DNA and Is Necessary for Meiotic Recombination
- Transmission of Hypervirulence Traits via Sexual Reproduction within and between Lineages of the Human Fungal Pathogen
- Integration of the Unfolded Protein and Oxidative Stress Responses through SKN-1/Nrf
- Guanine Holes Are Prominent Targets for Mutation in Cancer and Inherited Disease
- Regulation of the Boundaries of Accessible Chromatin
- Natural Genetic Transformation Generates a Population of Merodiploids in
- Ablating Adult Neurogenesis in the Rat Has No Effect on Spatial Processing: Evidence from a Novel Pharmacogenetic Model
- Genotype-Environment Interactions Reveal Causal Pathways That Mediate Genetic Effects on Phenotype
- The Molecular Mechanism of a -Regulatory Adaptation in Yeast
- Phenotypic and Genetic Consequences of Protein Damage
- Recent Acquisition of by Baka Pygmies
- Fatty Acid Taste Signals through the PLC Pathway in Sugar-Sensing Neurons
- A Critical Role for PDGFRα Signaling in Medial Nasal Process Development
- Chromatin-Specific Regulation of Mammalian rDNA Transcription by Clustered TTF-I Binding Sites
- Meiotic Recombination in Arabidopsis Is Catalysed by DMC1, with RAD51 Playing a Supporting Role
- dTULP, the Homolog of Tubby, Regulates Transient Receptor Potential Channel Localization in Cilia
- Widespread Dysregulation of Peptide Hormone Release in Mice Lacking Adaptor Protein AP-3
- , a Direct Transcriptional Target, Modulates T-Box Factor Activity in Orofacial Clefting
- PLOS Genetics
- Archív čísel
- Aktuálne číslo
- Informácie o časopise
Najčítanejšie v tomto čísle- A Genome-Wide Systematic Analysis Reveals Different and Predictive Proliferation Expression Signatures of Cancerous vs. Non-Cancerous Cells
- Recent Acquisition of by Baka Pygmies
- The Condition-Dependent Transcriptional Landscape of
- Histone Chaperone NAP1 Mediates Sister Chromatid Resolution by Counteracting Protein Phosphatase 2A
Prihlásenie#ADS_BOTTOM_SCRIPTS#Zabudnuté hesloZadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
- Časopisy