Skip to main content
SpringerLink
Log in

Whole transcriptome responses among females of the filariasis and arbovirus vector mosquito Culex pipiens implicate TGF-β signaling and chromatin modification as key drivers of diapause induction

  • Original Paper
  • Published:
Functional & Integrative Genomics Aims and scope Submit manuscript

Abstract

Culex pipiens mosquitoes are important disease vectors inhabiting temperate zones, worldwide. The seasonal reduction in temperature and photoperiod accompanying late summer and early fall prompts female mosquitoes to enter diapause, a stage of developmental arrest and physiological conditioning that enhances survival during the winter months. To investigate the molecular mechanisms underlying diapause induction, we used custom whole transcriptome microarrays to identify differences in gene expression following exposure to nondiapause (long days, 25 °C) and diapause-inducing (short days, 18 °C) environmental conditions. Using a two-way ANOVA, we identified 1130 genes that were differentially expressed. We used the expression of these genes across three time points to construct a gene co-expression network comprising five modules. Genes in modules 1, 2, and 3 were largely up-regulated, while genes in modules 4 and 5 were down-regulated when compared to nondiapause conditions. Pathway enrichment analysis of the network modules revealed some potential regulatory mechanisms driving diapause induction. Module 1 was enriched for genes in the TGF-ß and Wnt signaling pathways; module 2 was enriched for genes involved in insect hormone biosynthesis, specifically, ecdysone synthesis; module 3 was enriched for genes involved in chromatin modification; and module 5 was enriched for genes in the circadian rhythm pathway. Our results suggest that TGF-β signaling and chromatin modification are key drivers for the integration of environmental signals into the diapause induction phase in C. pipiens mosquitoes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Ahringer J (2000) NuRD and SIN3 histone deacetylase complexes in development. Trends Genet 16:351–356

    Article  CAS  PubMed  Google Scholar 

  • Arensburger P, Megy K, Waterhouse RM et al (2010) Sequencing of Culex quinquefasciatus establishes a platform for mosquito comparative genomics. Science 330:86–88

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Royal Stat Soc Ser B 57:289–300

    Google Scholar 

  • Benoit JB, Denlinger DL (2007) Suppression of water loss during adult diapause in the northern house mosquito, Culex pipiens. J Exp Biol 210:217–226

    Article  PubMed  Google Scholar 

  • Bolstad BM, Irizarry RA, Astrand M, Speed TP (2003) A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19:185–193

    Article  CAS  PubMed  Google Scholar 

  • Bünning E (1936) Die endogene tagesrhythmik als grundlage der photoperiodischen reaktion. Ber Dtsch Bot Ges 54:590–607

    Google Scholar 

  • Denlinger DL (2002) Regulation of diapause. Annu Rev Entomol 47:93–122

    Article  CAS  PubMed  Google Scholar 

  • Eldridge BF (1968) The effect of temperature and photoperiod on blood-feeding and ovarian development in mosquitoes of the Culex pipiens complex. Am J Trop Med Hyg 17:133–140

    CAS  PubMed  Google Scholar 

  • Fonseca DM, Keyghobadi N, Malcolm CA, Mehmet C, Schaffner F, Mogi M, Fleischer RC, Wilkerson RC (2004) Emerging vectors in the Culex pipiens complex. Science 303:1535–1538

    Article  CAS  PubMed  Google Scholar 

  • Harb M, Faris R, Gad AM, Hafez ON, Ramzy R, Buck AA (1993) The resurgence of lymphatic filariasis in the Nile delta. B World Health Organ 71:49–54

    CAS  Google Scholar 

  • Inoue T, Thomas JH (2000) Targets of TGF-b signaling in Caenorhabditis elegans dauer formation. Dev Biol 217:192–204

    Article  CAS  PubMed  Google Scholar 

  • Kanehisa M, Goto S (2000) KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28:27–30

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kanehisa M, Goto S, Sato Y, Kawashima M, Furumichi M, Tanabe M (2014) Data, information, knowledge and principle: back to metabolism in KEGG. Nucleic Acids Res 42:D199–D205

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kang DS, Denlinger DL, Sim C (2014) Suppression of allatotropin simulates reproductive diapause in the mosquito Culex pipiens 64: 48–53

  • Langfelder P, Horvath S (2008) WGCNA: an R package for weighted correlation network analysis. BMC Bioinform 9:559

    Article  Google Scholar 

  • Lawson D, Arensburger P, Atkinson P, Besansky NJ, Bruggner RV, Butler R, Campbell KS, Christophides GK, Christley S, Dialanas E et al (2009) VectorBase: a data resource for invertebrate vector genomics. Nucleic Acids Res 37:583–587

    Article  Google Scholar 

  • Mattingly PF, Rozeboom LE, Knight KL, Laven H, Drummond FH, Christophers SR, Shute PG (1951) The Culex pipiens complex. Trans R Ent Soc Lond 102:331–382

    Article  Google Scholar 

  • Mitchell CJ (1983) Differentiation of host-seeking behavior from blood-feeding behavior in overwintering Culex pipiens (Diptera: Culicidae) and observations on gonotrophic dissociation. J Med Entomol 20:157–163

    Article  CAS  PubMed  Google Scholar 

  • Ng H-H, Bird A (2000) Histone deacetylases: silencers for hire. Trends Biochem Sci 25:121–126

    Article  CAS  PubMed  Google Scholar 

  • Nguyen M, Parker L, Arora K (2000) Identification of maverick, a novel member of the TGF-β superfamily in Drosophila. Mech Develop 95:201–206

    Article  CAS  Google Scholar 

  • Ravasz E, Somera AL, Mongru DA, Oltvai ZN, Barabási AL (2002) Hierarchical organization of modularity in metabolic networks. Science 297:1551–1555

    Article  CAS  PubMed  Google Scholar 

  • Rhinehart JP, Robich RM, Denlinger DL (2006) Enhanced cold and desiccation tolerance in diapausing adults of Culex pipiens, and a role for Hsp70 in response to cold shock but not as a component of the diapause program. J Med Entomol 43:713–722

    Article  Google Scholar 

  • Robich RM, Denlinger DL (2005) Diapause in the mosquito Culex pipiens evokes a metabolic switch from blood feeding to sugar gluttony. PNAS 102:15912–15917

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Robich RM, Rinehart JP, Kitchen LJ, Denlinger DL (2007) Diapause-specific gene expression in the northern house mosquito, Culex pipiens L., identified by suppressive subtractive hybridization. J Insect Physiol 53:235–245

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Schuettengruber B, Martinez A-M, Iovino N, Cavalli G (2011) Trithorax group proteins: switching genes on and keeping them active. Nat Rev Mol Cell Bio 12:799–814

    Article  CAS  Google Scholar 

  • Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Siebold AP, Banerjee R, Tie F, Kiss DL, Moskowitz J, Harte PJ (2009) Polycomb repressive complex 2 and trithorax modulate Drosophila longevity and stress resistance. Proc Natl Acad Sci U S A 107:169–174

    Article  PubMed Central  PubMed  Google Scholar 

  • Sim C, Denlinger DL (2008) Insulin signaling and FOXO regulate the overwintering diapause of the mosquito Culex pipiens. PNAS 105:6777–6781

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sim C, Denlinger DL (2009) A shut-down in expression of an insulin-like peptide, ILP-1, halts ovarian maturation during the overwintering diapause of the mosquito Culex pipiens. Insect Mol Bio 18:325–332

    Article  CAS  Google Scholar 

  • Sim C, Denlinger DL (2013) Insulin signaling and the regulation of insect diapause. Front Physiol 4:189

    Article  PubMed Central  PubMed  Google Scholar 

  • Smoot M, Ono K, Johannes Ruscheinski J, Wang P-L, Ideker T (2011) Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics 27:431–432

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Spielman A (1974) Effect of synthetic juvenile hormone on ovarian diapause of Culex pipiens mosquitoes. J Med Entomol 11:223–225

    Article  CAS  PubMed  Google Scholar 

  • Spielman A, Wong J (1973) Environmental control of ovarian diapause in Culex pipiens. Ann Entomol Soc Am 66:905–907

    Article  Google Scholar 

  • Sturn A, Quackenbush J, Trajanoski Z (2002) Genesis: cluster analysis of microarray data. Bioinformatics 18:207–208

    Article  CAS  PubMed  Google Scholar 

  • Untergasser A, Nijveen H, Rao X, Bisseling T, Geurts R, Leunissen JA (2007) Primer3Plus, an enhanced web interface to Primer3. Nucleic Acids Res 35:W71–W74

    Article  PubMed Central  PubMed  Google Scholar 

  • Vinogradova EB (2000) Culex pipiens pipiens mosquitoes: taxonomy, distribution, ecology, physiology, genetics, applied importance and control. Pensoft, Sofia

  • Wang J, Duncan D, Shi Z, Zhang B (2013) WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013. Nucleic Acids Res 41:W77–W83

    Article  PubMed Central  PubMed  Google Scholar 

  • Waterhouse RM, Tegenfeldt F, Li J, Zdobnov EM, Kriventseva EV (2013) OrthoDB: a hierarchical catalog of animal, fungal and bacterial orthologs. Nucleic Acids Res 41:D358–D365

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang B, Kirov SA, Snoddy JR (2005) WebGestalt: an integrated system for exploring gene sets in various biological contexts. Nucleic Acids Res 33:W741–W748

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Ryan Hemme for collecting the larvae used in establishment of the C. pipiens South Bend strain. We also thank Melissa Stephens in the University of Notre Dame Genomics Core Facility for processing the microarrays. This work was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (RO1-AI079125-A1) to D.W.S.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, 107C Galvin Life Sciences, Notre Dame, IN, 46556, USA

    Paul V. Hickner, Akio Mori, John C. Tan & David W. Severson

  2. Department of Computer Science and Engineering, University of Notre Dame, Notre Dame, IN, 46556, USA

    Erliang Zeng

Authors
  1. Paul V. Hickner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akio Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Erliang Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John C. Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David W. Severson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David W. Severson.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(GIF 9 kb)

High resolution image (TIFF 254 kb)

ESM 2

(DOCX 14 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hickner, P.V., Mori, A., Zeng, E. et al. Whole transcriptome responses among females of the filariasis and arbovirus vector mosquito Culex pipiens implicate TGF-β signaling and chromatin modification as key drivers of diapause induction. Funct Integr Genomics 15, 439–447 (2015). https://doi.org/10.1007/s10142-015-0432-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10142-015-0432-5

Keywords

Search

Navigation