CHARACTERIZING THE ROLE OF LRIG1 IN THE DEVELOPMENT OF THE COLONIC EPITHELIUM
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Date
2024-01-09
Authors
Hopton, Rachel
Journal Title
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Publisher
University of Oregon
Abstract
The digestive system is essential for many higher-order organisms to absorb nutrients and secrete waste. For mammals, the digestive tract develops as a continuous tube along the rostral-caudal axis and is split into two regions, the small intestine and the large intestine. These two sections form two discrete organs, which differ in structure and function. At the cellular level, each section has its own specific composition of epithelial cell types, which enables the small and large intestine to serve distinct roles in digestion. The large intestine is also known as the colon, and its primary functions are to serve as a barrier to the microbe-rich external environment, to absorb water, and to secrete waste. The colonic epithelium is lined with test tube-shaped invaginations called crypts of Lieberkühn, comprised of stem, progenitor, and differentiated cells which facilitate these absorptive and secretory functions of the adult colon. In the mouse, growth and specification of the intestine occurs in utero and completes after birth. The small intestine develops embryonically whereas the colon develops after the mouse is born (postnatally). While a great deal is known about the growth and specification of the small intestine, less is known about the molecular cues that define the structural and cellular parameters for colon crypt formation.
The primary goal of my thesis is to define the cellular, morphological, and molecular features of colon crypt development during the first three weeks after birth. In this thesis, I characterized the organization of colonic epithelial cells, areas of proliferation, and emergence and expression of a stem and progenitor marker, Lrig1. I show cells expressing Lrig1 are present when the mouse is born and these cells behave as stem cells throughout colon development. To interrogate the requirements for normal mouse colon development, I use an inducible knockout mouse to eliminate Lrig1, and demonstrate this leads to an increase in epithelial cell proliferation. Further, I show loss of Lrig1 does not impact differentiation in the developing colon up to two weeks after birth. My thesis contributes to the understanding of normal mouse colon development and highlights specific molecular requirements for normal colon crypt development.
This dissertation includes previously published co-authored material.
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Keywords
Colon Development, Lrig1, Stem cell