All ETDs from UAB

Advisory Committee Chair

Natalia Kedishvili

Advisory Committee Members

Shannon M Bailey

Karen L Gamble

Kelly Nichols

Nabiha Yusuf

Rui Zhao

Document Type

Dissertation

Date of Award

2022

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

The bioactive form of vitamin A, retinoic acid is essential for development, cellular differentiation, epigenetic modifications, the immune system, and a variety of other processes due to its ability to regulate over 500 genes through activation of nuclear receptors. While many studies have focused on characterizing the biosynthesis and signaling of retinoic acid in embryogenesis, few have focused on adult tissues. Recent research has identified a novel retinol dehydrogenase, retinol dehydrogenase epidermal 2 (RDHE2), and shown RDHE2 is a potent, physiologically relevant retinol dehydrogenase in Xenopus. The work in this dissertation characterizes RDHE2 in mammalian models. We identify a paralog of RDHE2, RDHE2-similar (RDHE2S; collectively, RDHEs), and demonstrate both enzymes are physiologically relevant in mice. Furthermore, we demonstrate that RDHEs are tissue-specific retinol dehydrogenases that contribute to both developmental processes and maintenance of adult tissues. RDHEs are most highly expressed in skin, and the absence of RDHEs affects hair follicle development and alters the progression of the hair cycle in adult mice. However, transcripts of RDHEs are expressed in a variety of other tissues, and their absence alters whole body composition with aging. Interestingly, absence of RDHEs does not phenocopy systemic vitamin A deficiency, despite lowering retinoic acid levels in skin. Overall, this dissertation characterizes RDHEs in mammals and demonstrates their capacity to regulate retinoic iv acid biosynthesis in a tissue-specific manner, the disruption of which causes novel and diverse effects.

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