Ruchi Bansal Doctoral Dissertation

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Cilia Associated Signaling In Adult Energy Homeostasis

thesis
posted on 09.09.2022, 14:28 authored by Ruchi BansalRuchi Bansal

  

Cilia are cell appendages that sense our environment and are critical in cell-to-cell communication. Dysfunction of cilia can result in several disease states including obesity. While cilia in the brain are known to be important for feeding behavior, it is unclear how they regulate energy homeostasis. Classically, cilia coordinate signaling through surface receptors called G-protein coupled receptors (GPCRs). For example, cilia mediated GPCR signaling is critical for both our senses of vision and smell. How cilia regulate the signaling of GPCRs in other areas of the body including the brain is only now emerging. To answer cell biology questions around cilia mediated GPCR signaling in neurons, we developed a system for primary neuronal cultures. We discovered that the cilia mediated hedgehog pathway influences the ability of neurons to respond to GPCR ligands. For the first time, this result highlights the role of the hedgehog pathway in neurons. We continue to explore how cilia integrate the hedgehog pathway and GPCR signaling in the central nervous system, and the potential connections to energy homeostasis. We discovered that hedgehog pathway activity in feeding centers of the brain changes based upon feeding conditions like fasting. We also learned that activating the hedgehog pathway in these brain regions is sufficient to cause obesity in mice. These novel results highlight an unrecognized role for the hedgehog pathway in the regulation of feeding behavior. Overall, this work provides a better understanding of ciliopathy associated obesity and may reveal more common mechanisms of obesity in the general population. In addition, this work implicates the hedgehog pathway in regulating behaviors and new modes of cell-cell communication within the central nervous system.

Funding

Ciliary Mchr 1 Signaling in Feeding Behavior and Obesity

National Institute of Diabetes and Digestive and Kidney Diseases

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Mchr1 Cilia Mediated Signaling

American Heart Association

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History

Degree Type

Doctor of Philosophy

Department

Biological Sciences

Campus location

Indianapolis

Advisor/Supervisor/Committee Chair

Nicolas F. Berbari

Additional Committee Member 2

Benjamin J. Perrin

Additional Committee Member 3

Teresa L. Mastracci

Additional Committee Member 4

Anthony J. Baucum

Additional Committee Member 5

Kenneth W. Dunn