Transcriptional regulation of gut epithelial lineages

Massachusetts General Hospital, Boston MA

Investigators

Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): Normal intestinal development is likely controlled by spatially and temporally precise activation of a few critical transcriptional regulators. Published data support the idea that the same transcriptional effectors are involved in pathologic cellular transformation in metaplasia and neoplasia. Despite the potential for these transcriptional mediators to serve as diagnostic and scientific tools in cancer and its precursors, the overall knowledge of molecular events that control gut differentiation is limited. With the potential for future clinical benefit in mind, the lab has identified 25 transcription factors (from a pool of nearly 1,000 known or predicted transcription factors) that are expressed in the developing fetal intestine but excluded from the stomach. This proposal aims 1) to use a combination of reverse transcription-polymerase chain reaction and in situ hybridization to identify a subset of these factors that is expressed exclusively in the developing intestinal epithelium and ectopically in two independent mouse models of intestinal metaplasia, and 2) to analyze the functional role of 2-3 selected factors by overexpressing them in cultured fetal stomach explants and assessing for aberrant induction of intestine-specific genes. This proposal serves as a prelude to more detailed in vivo studies involving engineered mouse models in the future. [unreadable] [unreadable]