Sophia Liang
Pronouns: she/her
Research Mentor(s): Katherine Walton
Co-Presenter:
Research Mentor School/College/Department: Internal Medicine- Gastroenterology Division / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 5 – 3:40pm – 4:30 pm
Room: League Ballroom
Authors: Katherine Walton, Sophia Liang
Presenter: 44
Abstract
Villi are finger-like projections that increase the small intestinal surface area to maximize nutrient absorption. Hedgehog ligands produced by the epithelium direct adjacent mesenchymal cells to aggregate (clusters), which coordinate villus emergence at mouse embryonic day 14.5 (E14.5). Hedgehog signaling affects cluster development where loss of signaling causes a complete lack of mesenchymal clusters and villi while overexpression increases cluster and villus size, but the exact mechanism is unknown. Previous research demonstrated that clusters and vasculature have reciprocal effects where changing the patterning of one alters the other. Because Hh signaling also regulates vascular development, we sought to determine if the role of Hh in cluster formation is affected by the changes in mesenchymal cluster cells or in the vasculature. Using genetic mouse lines, Hh signaling was altered in endothelial cells (Gata2-CreER) or in Hh responsive cells of the cluster (Gli1CreERT2). Loss of Hh signaling was induced by conditional deletion of Smoothened floxed alleles. Hh signaling was increased by conditional activation of R26-rTTA (removal of a floxed stop site) which in the presence of doxycycline drives expression of activated Gli2 (R26-rTTA; TetO-Gli2A). Tamoxifen and doxycycline were fed to pregnant females prior to cluster formation in the developing fetuses. Intestines were harvested at E16 and alterations in cluster and vascular development were assessed by immunostaining thick sections of intestine to mark mesenchymal cluster cells (anti-PDGFRa) and epithelial cells (anti-Ecadherin). Preliminary findings indicate that altering Hh signaling in the mesenchymal clusters results in significant changes in cluster formation and vascular patterning while altering Hh signaling in endothelial cells at this stage of development did not produce apparent changes. The information gained from these studies adds to our understanding of how Hh signaling regulates cluster formation and villus development furthering the ultimate goal of inducing villus development in patients with compromised absorptive function.
Biomedical Sciences, Interdisciplinary
