Saad Qureshi
Pronouns: he/him
Research Mentor(s): Katherine Walton
Co-Presenter:
Research Mentor School/College/Department: Internal Medicine- Gastroenterology Division / Medicine
Presentation Date: April 20
Presentation Type: Oral5
Session: Session 5 – 3:40pm – 4:30 pm
Room: Breakout Room 4
Authors: Saad Qureshi, Katherine Walton
Presenter: 1
Abstract
The Hedgehog (Hh) signaling pathway is fundamental in morphogenesis of a variety of organs. In the small intestine, Hh signaling is required for villus development. Villi are finger-like projections that increase the absorptive surface area of the small intestine. When villi form, mesenchymal cells are signaled by Hh ligands to begin clustering under the epithelium of the intestine. Hedgehog signaling determines cluster pattern where loss of Hh results in no clusters and increased Hh results in larger clusters. Clusters then direct the emergence of villi which mirror the pattern and size of the clusters. Because previous studies globally altered Hh signaling, it is currently unknown exactly which Hh responsive cell type of the mesenchymal cluster is responsible for altered villus formation. This project investigates the effects of conditionally decreasing Hh signaling in vivo using the Smof/f; Gli1CreERT2 transgenic mouse line with dosing of tamoxifen from embryonic day (E) 10.5 to 12.5 (prior to cluster formation) and examines which specific cell types of the mesenchymal cluster were recombined by Gli1CreER in a mouse reporter line (mT/mG). Overall growth of the intestine was observed with loss of Hh signaling as intestinal length normalized to body length was decreased beginning at E15.5. With the use of antibody staining to highlight specific cell types and confocal microscopic imaging, tissue sections were reconstructed in three-dimensions to visualize villus structures and mesenchymal cell types. Similar to previous studies with global loss of Hh signaling, genetic loss of Hh signaling in Hh responsive cells resulted in a loss of cluster formation and villus emergence. Furthermore, the specific cell types that are recombined in this model include fibroblasts and PDGFRa expressing cells of the cluster and smooth muscle cells in the inner circular muscle layer, but not immune cells, nerve cells or endothelial cells.
Biomedical Sciences, Interdisciplinary
