Insulin-like peptides and the target of rapamycin pathway coordinately regulate blood digestion and egg maturation in the mosquito Aedes aegypti

PLoS One. 2011;6(5):e20401. doi: 10.1371/journal.pone.0020401. Epub 2011 May 27.


Background: Mosquitoes are insects that vector many serious pathogens to humans and other vertebrates. Most mosquitoes must feed on the blood of a vertebrate host to produce eggs. In turn, multiple cycles of blood feeding promote frequent contacts with hosts and make mosquitoes ideal disease vectors. Both hormonal and nutritional factors are involved in regulating egg development in the mosquito, Aedes aegypti. However, the processes that regulate digestion of the blood meal remain unclear.

Methodology/principal findings: Here we report that insulin peptide 3 (ILP3) directly stimulated late phase trypsin-like gene expression in blood fed females. In vivo knockdown of the mosquito insulin receptor (MIR) by RNA interference (RNAi) delayed but did not fully inhibit trypsin-like gene expression in the midgut, ecdysteroid (ECD) production by ovaries, and vitellogenin (Vg) expression by the fat body. In contrast, in vivo treatment with double-stranded MIR RNA and rapamycin completely blocked egg production. In vitro experiments showed that amino acids did not simulate late phase trypsin-like gene expression in the midgut or ECD production by the ovaries. However, amino acids did enhance ILP3-mediated stimulation of trypsin-like gene expression and ECD production.

Conclusions/significance: Overall, our results indicate that ILPs from the brain synchronize blood meal digestion and amino acid availability with ovarian ECD production to maximize Vg expression by the fat body. The activation of digestion by ILPs may also underlie the growth promoting effects of insulin and TOR signaling in other species.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aedes / cytology
  • Aedes / embryology
  • Aedes / metabolism*
  • Aedes / physiology
  • Amino Acids / metabolism
  • Animals
  • Blood / metabolism*
  • Digestion* / genetics
  • Ecdysteroids / biosynthesis
  • Female
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Insect Proteins / metabolism*
  • Insulin / metabolism*
  • Oviposition / genetics
  • Ovum / growth & development*
  • Ovum / physiology
  • Receptor, Insulin / deficiency
  • Receptor, Insulin / genetics
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism*
  • Trypsin / metabolism
  • Vitellogenesis / genetics


  • Amino Acids
  • Ecdysteroids
  • Insect Proteins
  • Insulin
  • TOR Serine-Threonine Kinases
  • Receptor, Insulin
  • Trypsin