The Role of Sox9 in the Enteroendocrine Lineage of the Small Intestine Epithelium (2008)

Undergraduate: Eric Formeister

Faculty Advisor: Scott Magness
Department: Biology

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The mammalian small intestine epithelium (SIE) consists of four differentiated cell types which collectively perform the absorptive and secretory functions that are essential for functional gut physiology in normal, diseased and injured states. Absorptive enterocytes and three secretory cell types (goblet, Paneth and enteroendocrine (EE) cells) are all produced from multi-potent stem and progenitor cells residing in epithelial invaginations called crypts. Characterizing the network of genes and molecular signaling pathways responsible for the precise control of each developmental pathway is important to understand the rapid proliferation and regeneration characteristic of this tissue type. The transcription factor SOX9 is essential for cell specification and maintenance of stem cell competence and potency in other tissue types, including the pancreas, cartilage and neural tissues. Using a Sox9 EGFP transgenic mouse model, our laboratory previously identified two distinct SOX9 expression patterns in the crypt epithelium where cells expressing high levels of SOX9 show enhanced expression of EE genes. To investigate the novel association between high levels of SOX9 in the crypt and the EE cell lineage, we studied Sox9 EGFP adult tissue sections with immunofluorescent experiments. SOX9 high-expressing crypt cells co-localized with mature EE markers but not the proliferation marker Ki67. Additionally, we used a lentiviral construct to over-express SOX9 in a rat SIE progenitor cell line. Cells expressing high levels of SOX9 appeared to stop proliferating and became terminally differentiated, producing morphologies resembling entero/neuroendocrine/ neural cells. These results yield new insights into the developmental pathway of the EE lineage.