Purdue University Graduate School
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KK Brewer-MS Thesis.pdf (2.45 MB)

DYNAMIC CILIARY LOCALIZATION IN THE MOUSE BRAIN

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posted on 2024-06-03, 18:56 authored by Katlyn M BrewerKatlyn M Brewer

Primary cilia are hair-like structures found on nearly all mammalian cell types, including cells in the developing and adult brain. Cilia establish a unique signaling compartment for cells. For example, a diverse set of receptors and signaling proteins localize within cilia to regulate many physiological and developmental pathways including the Hh pathway. Defects in cilia structure, protein localization, or cilia function lead to genetic disorders called ciliopathies, which present with various clinical features including several neurodevelopmental phenotypes and hyperphagia associated obesity. Despite their dysfunction being implicated in several disease states, understanding their roles in CNS development and signaling has proven challenging. I hypothesize that dynamic changes to ciliary protein composition contributes to this challenge and may reflect unrecognized diversity of CNS cilia. The proteins ARL13B and ADCY3 are established ciliary proteins in the brain and assessing their localization is often used in the field to visualize cilia. ARL13B is a regulatory GTPase important for regulating cilia structure, protein trafficking, and Hh signaling, while ADCY3 is a ciliary adenylyl cyclase thought to be involved in ciliary GPCR singaling. Here, I examine the ciliary localization of ARL13B and ADCY3 in the perinatal and adult mouse brain by defining changes in the proportion of cilia enriched for ARL13B and ADCY3 depending on brain region and age. Furthermore, I identify distinct lengths of cilia within specific brain regions of male and female mice. As mice age, ARL13B cilia become relatively rare in many brain regions, including the hypothalamic feeding centers, while ADCY3 becomes a prominent cilia marker. It is important to understand the endogenous localization patterns of these proteins throughout development and under different physiological conditions as these common cilia markers may be more dynamic than initially expected. Understanding regional and development associated cilia signatures and physiological condition cilia dynamic changes in the CNS may reveal molecular mechanisms associated with ciliopathy clinical features such as obesity.

Funding

Ciliary Mchr 1 Signaling in Feeding Behavior and Obesity

National Institute of Diabetes and Digestive and Kidney Diseases

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History

Degree Type

  • Master of Science

Department

  • Biological Sciences

Campus location

  • Indianapolis

Advisor/Supervisor/Committee Chair

Nicolas F. Berbari

Additional Committee Member 2

Teresa Mastracci

Additional Committee Member 3

Lata Balakrishnan