Author ORCID Identifier

0000-0001-9449-2269

Date of Graduation

5-2018

Document Type

Dissertation (PhD)

Program Affiliation

Genes and Development

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Andrew B. Gladden

Committee Member

Russell Broaddus

Committee Member

Richard Behringer

Committee Member

Rachel Miller

Committee Member

David Loose

Abstract

Apicobasal polarity and cell adhesion are necessary for the proper formation and organization of epithelial tissues. Merlin couples cell polarity and adhesion through correct localization of the polarity protein Par3 and maturation of apical junctions. Merlin and Par3 are necessary for the development and homeostasis of highly regenerative tissues like the epidermis. The continual repopulation of the endometrium after each menstrual cycle requires a constant reorganization of cell polarity and adhesion. The endometrium consists of a luminal epithelium that postnatally gives rise to the distinct glandular epithelium. Endometrial glands are necessary to secrete nutrients for the pre-implantation embryo. In addition, the endometrial gland is thought to be where endometrial cancer originates. While the endometrium is important for female fertility, relatively little is understood about how glands develop or how endometrial cancer forms. We examine the role of Merlin and apicobasal polarity in endometrial development and homeostasis. We determine that Merlin regulation of apicobasal polarity is necessary for proper endometrial gland formation. Apicobasal polarity is disrupted in low-grade endometrial cancer and mediates Notch regulated proliferation and migration in endometrial cancer cells. This dissertation reveals a critical role for Merlin and cell polarity in endometrial gland development, mammalian fertility, and endometrial cancer.

Keywords

Endometrium, Endometrial cancer, Apicobasal Polarity, Merlin, Cell Adhesion, Endometrial Glands, Uterus, Uterine Development

Available for download on Saturday, March 30, 2019

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