Genetic circuitry of early embryos provides targets for population replacement strategies, which have important potential applications in the control of disease vectors such as mosquitoes. However, mosquito development remains poorly understood because current research in this group focuses on human disease vectors in which a tough and heavily pigmented eggshell hinders functional developmental studies. The research goal of this proposal is to elucidate the genetic mechanism that determines anterior-to-posterior (AP) polarity in embryos of the culicomorphan mosquito Chironomus riparius (syn. C. thummi). In Chironomus, a range of experimental perturbations can lead to complete or partial axis inversions (mirror image double abdomens or double heads), which may also occur spontaneously. These observations suggest that AP polarity in early mosquito embryos is very labile. Furthermore, mosquitoes lack the homeobox gene bicoid, which determines embryonic AP polarity in the fruit fly Drosophila (a key model for insect development). We have established efficient protocols for studying gene expression and function (RNA interference, mRNA injection) in Chironomus riparius, providing the tools for testing the ability of candidate genes to prevent axis inversions in a mosquito model.
The specific aims of this proposal are to (1) to test Chironomus homologues of genes that have been implicated in early AP axis specification in other insects for their ability to prevent or induce mirror image duplications of the head or abdomen, and (2) to determine how these genes regulate each other. The experiments will result in a model for AP axis specification in Chironomus embryos that might be generally applicable for mosquitoes.

Public Health Relevance

Chironomus provides a new experimental system on the mosquito branch. It is amenable to functional genetic studies in early embryos and should therefore help to understand differences in embryonic development between Drosophila and medically relevant culicomorphan mosquitoes such as the vectors of Malaria (Anopheles), Yellow fever (Aedes) and River blindness (Simulium). As head-to-tail polarity in early embryos of this group is easily perturbed, the underlying genetic mechanism could be a suitable target for combating medically relevant species.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
5R03HD067700-02
Application #
8322701
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Mukhopadhyay, Mahua
Project Start
2011-09-01
Project End
2013-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
2
Fiscal Year
2012
Total Cost
$78,000
Indirect Cost
$28,000
Name
University of Chicago
Department
Biology
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637