The Neuropeptide Regulation of Host-Seeking Behavior in Aedes Aegypti Mosquitoes

<p>Aedes aegypti mosquitoes are the principal vectors for several human diseases including Dengue Fever, which causes ~400 million cases and ~24,000 deaths per year (Bhatt et al., 2013; WHO, 2002). Novel strategies to combat mosquito-borne diseases are needed for A. aegypti and other mosquitoes such as the malaria vector Anopheles gambiae. Our goal was to discover new ways to interfere with the ability of a mosquito to locate a human host for a blood meal. Currently, the mechanistic basis of host-seeking and its regulation remain incompletely understood. Although it is known that mosquitoes require human odor cues to locate a human host, the critical odor components and associated olfactory receptors have not been identified (Klowden, 1995; Takken and Knols, 1999). Previous work showed that mosquito host-seeking behavior is inhibited by a hemolymph-borne humoral factor for three days following a blood meal. Subsequent studies identified Head Peptide-I as a candidate neuropeptide modulating this suppression in host-seeking behavior. This conclusion was strengthened by the observation that Head Peptide-I injection into non-blood-fed females triggered the inhibition of host-seeking. The mechanism by which this important peptide alters mosquito behavior and the receptor through which it signals are unknown (Brown et al., 1994). We used a cell-based calcium-imaging screen to identify the G-protein coupled receptor NPY-Like Receptor-1 (NPYLR1) as a candidate Head Peptide-I receptor. We found that multiple NPYLR1 agonists, including the feeding-related Short-Neuropeptide-3 (sNPF3), are capable of inhibiting host-seeking behavior when injected into non-blood-fed females. To investigate whether NPYLR1 is required for Head Peptide-I inhibition, we pioneered targeted mutagenesis with zinc-finger nucleases to create multiple NPYLR1 null-mutant mosquito lines. We predicted that these mutants would no longer show inhibition of host-seeking behavior after a blood meal. While we can say with certainty that NPYLR1 is a receptor for Head Peptide-I, we found no behavioral effects for NPYLR1 mutants in locomotion, egg-laying, sugar feeding, blood feeding, or host-seeking behavior. Our results suggest that NPYLR1 is not required in vivo for Head Peptide-I action and that a redundant signaling mechanism for behavioral inhibition exists. Future work will determine the necessity of Head Peptide-I during host-seeking inhibition and attempt to identify additional Head Peptide-I and sNPF receptors. This research will clarify the mechanism of Head Peptide-I inhibition and could form the basis for novel strategies to control mosquito host-seeking behavior.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Thesis

Year

2014

Author dc:creator

• Liesch, Jeff

Contributors dc:contributor

• Leslie B. Vosshall

• mosquito behavior
• host-seeking
• Aedes aegypti
• Head Peptide-I
• NPYLR1
• neuropeptide signaling
• Life Sciences

Repository record dc:identifier

https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/221

OAI identifier oai:identifier

oai:digitalcommons.rockefeller.edu:student_theses_and_dissertations-1223