Multifaceted Control of Pancreatic Development by Mesenchymal Regulators of Hedgehog Signaling
Year: 2018
Type: dissertation
Abstract: Pancreatic development is coordinated by signaling pathways through dynamic epithelial-mesenchymal interactions that remain poorly understood. My work investigates epithelial-mesenchymal cross-talk underlying digestive organ development and reveals the existence of organ-specific mesenchymal niche signals as well as the specific downregulation of Hedgehog signaling in the pancreatic mesenchyme. Signaling activation via loss of Hedgehog negative regulators Sufu and/or Spop in the mesenchyme, but not the epithelium, severely inhibits pancreatic growth and endocrine differentiation through shifting mesenchymal identity towards a more gastrointestinal fate. Despite required downregulation by Sufu and Spop, mesenchymal Hedgehog signaling is still required as inactivation leads to malformations resembling the congenital disorder, annular pancreas. Altogether, my work demonstrates that the fine tuning of mesenchymal Hedgehog signaling by negative regulators, Sufu and Spop, is critical for proper pancreatic development and the establishment of organ-specific mesenchymal niches.
Source: TSpace (University of Toronto)
Author: Theodora Yung
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3138026710