Insights Into the Development of Gastrointestinal Brunner's Glands: Critical Stem Cells and Differentiation Factors
Loading...
Date
2016-05
Authors
Parappilly, Michael
Journal Title
Journal ISSN
Volume Title
Publisher
University of Oregon
Abstract
Gastrointestinal Brunner's Glands are composed of secretory glandular
epithelium and are located at the junction between the pylorus of the stomach and the
duodenum of the small intestine. Brunner's Glands function by secreting a mucous-rich
substance containing sodium bicarbonate and other important proteins in order to
neutralize stomach acid and prevent damage to the intestinal epithelium. Prior research
has shown that Brunner's Glands develop after birth, but little is known about the
molecular mechanisms that control their development. Tumors of the in Brunner's
Glands are known to occur in humans and understanding their developmei:it may assist
in understanding how cancer and other pathologies in this gland arises. The aim of this
study is to evaluate the stem cells and proteins that contribute to the development of the
gland by using the laboratory mouse as our model organism.
A stem cell marker known as Lrig I is a regulator of intestinal stem cell
development and by using a technique known as "developmental lineage tracing," we
have shown that Lrigl expressing stem cells contribute to the development of the
Brunner's Gland. Developmental lineage tracing was also used in order to test for the contribution of Villin to the formation of the Brunner’s Gland, and this is another
intestinal marker important for differentiation. Our results showed that Brunner’s
Glands do not express Villin. In addition, since Brunner’s Glands are secretory glands,
we hypothesized that a transcription factor called SPDEF is critical for proper
development as it is an important protein for secretory gland formation. By analyzing
the small intestines of transgenic mice with SPDEF mutations at multiple stages of
maturity, we find that Brunner’s Glands were largely deformed and underdeveloped.
These findings suggest that Brunner’s Glands are more closely related to the
gastric epithelium, rather than the intestinal epithelium as has been previously
postulated. Overall, the results of this study provide insight into the specific progenitor
cells that contribute developmentally to the Brunner’s Gland, and shed light on the
molecular mechanisms important for proper formation.
Description
37 pages. A thesis presented to the Department of Human Physiology and the Clark Honors College of the University of Oregon in partial fulfillment of the requirements for degree of Bachelor of Science, Spring 2016.
Keywords
Brunner's glands, Development, Molecular biology, Stem cells, Intestine, Differentiation factors