Graduation Date

Fall 12-19-2025

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Molecular Genetics & Cell Biology

First Advisor

Subu Ramanathan, PhD

Abstract

The stem and Paneth cells in the intestinal crypt are arranged in a checkerboard-like pattern. The contact between stem cells and Paneth cells plays a critical role in the maintenance and function of the intestinal stem cell niche. However, the physical and molecular principles underlying the maintenance of the checkerboard pattern are mostly unknown. Previous studies indicate that discrepancies in cell size control epithelial organization. We find that the stem cells are approximately 3.5 times smaller than Paneth cells. This study will determine if cell size discrepancy in the intestinal crypt has a causal role in generating checkerboard order-like organization. To interrogate the role of cell size in intestinal organization, we developed a stem cell mouse model to knock out Tsc1, a negative regulator of the mTOR pathway, to increase stem cells size, reduce the discrepancy in cell size, and determine its effect on checkerboard organization in the crypt. Upon Tsc1 knockout in stem cells, there was a decrease in size discrepancy and an increase in proliferation, accompanied by disruption of crypt organization. Interestingly, adhesion proteins: E-cadherin, beta-catenin, F-actin, and Nectin 3 enrichment at the crypt cells’ junctions were largely homogeneous between different cell types, indicating that they are unlikely to contribute to crypt organization. Altogether, our studies find that differential cell size and proliferation between Paneth and stem cells are drivers of crypt organization.

Comments

2025 Copyright, the authors

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Available for download on Wednesday, December 01, 2027

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