Date on Senior Honors Thesis

5-2019

Document Type

Senior Honors Thesis

Degree Name

B.S.

Department

Biology

Degree Program

College of Arts and Sciences

Author's Keywords

retinoic acid; salivary gland development; angiogenesis; ctgf; rdh10

Abstract

Salivary gland hypofunction is a major disorder of salivary glands, and can arise either from diseases such as xerostomia, or from defective epithelial morphogenesis during embryogenesis. Hundreds of thousands of individuals suffer from dry mouth, and there is currently no restorative therapy for these patients. Investigation of salivary gland developmental biology will inform regenerative therapies. Currently it is known that retinoic acid (RA), the biologically active form of Vitamin A, is required for proper development of the salivary gland, but little is known about its cellular mechanism regulating organogenesis. This study sought to analyze salivary gland development in Rdh10 knock down mice to determine if vascular development is impaired, to quantify expression of candidate genes known to be both targets of RA signaling and be involved in angiogenesis, and then identify novel angiogenic genes. We show that retinoic acid signaling alters expression of genes involved in angiogenesis in Rdh10 knockdowns. Using RNAscope, immunocytochemistry, and qPCR, we characterize the expression and location of Ctgf and its protein product, a gene known to aid blood vessel formation. This is the first study to characterize a vascular phenotype associated with Rdh10 mutants, and identify angiogenic gene targets of RA signaling in Rdh10 mutants.

Lay Summary

Vitamin A is necessary for many organisms to develop salivary glands, including humans and mice. However, the biomolecular mechanism for this observation is not fully known. This study hypothesizes that Vitamin A in its active form turns on genes important for blood vessel formation which enables proper growth of embryonic salivary glands. This study has confirmed that when a mouse embryo cannot properly metabolize Vitamin A, five genes critical for blood vessel formation are not turned on and continuous blood vessels in their salivary glands do not form. Additionally, this study has detailed how much certain genes are turned on with healthy Vitamin A influence, and where the transcripts and proteins of one of those genes reside in a developing salivary gland.This information can guide future projects to characterize the five genes identified in this study to gain more knowledge of how a salivary gland forms and ultimately develop regenerative therapies for humans with low-functioning salivary glands.

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