Summary:
Neuromedin U (NMU) is a highly conserved and multifunctional neuropeptide with pleiotropic roles in muscle contraction, blood pressure regulation, pain perception, appetite control, thermogenesis, bone growth, and drug-reward response. NMU acts via NMU receptors, which are target receptors for obesity and inflammatory disorders. The Drosophila genes CAPA and Hugin encode NMU-like peptides which act via conserved NMU-like receptors. Our lab has recently carried out an RNA interference screen for neuropeptides required for proper pupariation, a complex innate behavior that occurs at the end of the larval growth phase and consists of stereotyped motor programs, which amongst other things, remodel the larval body into the puparium, a structure that protects the animal from desiccation and predators during metamorphosis. The lack of CAPA and/or Hugin function leads to long and thin puparia that are easily identifiable by eye and distinguished quantitatively from controls by their puparium aspect ratio (length/width). This provides a cheap and precise in vivo model to study the NMU pathway and to assay for drugs that act as agonists or antagonists of the pathway. This project aims to explore and refine our preliminary findings on the roles of CAPA and Hugin during pupariation, including the definition of redundant and specific roles of each gene. This will include the generation of CAPA and Hugin double mutants using precise genome editing. We also plan to use state-of-the-art neurogenetics to identify the neurons that are required for CAPA and Hugin function during pupariation. We believe the refinement of this pupariation model can lead to a reliable assay for NMU-like activity, which will be of interest for drug testing to multiple fields, including obesity and inflammatory diseases.
Funding Institution:
Fundação para a Ciência e a Tecnologia
Keywords:
neuronal circuit, neuropeptide, behavior, obesity - Neuropéptido, obesidade, comportamento, circuito neuronal
