title: Epithelial dynamics of pancreatic branching morphogenesis.
abstract: The mammalian pancreas is a highly branched gland, essential for both digestion and glucose homeostasis. Pancreatic branching, however, is poorly understood, both at the ultrastructural and cellular levels. In this article, we characterize the morphogenesis of pancreatic branches, from gross anatomy to the dynamics of their epithelial organization. We identify trends in pancreatic branch morphology and introduce a novel mechanism for branch formation, which involves transient epithelial stratification and partial loss of cell polarity, changes in cell shape and cell rearrangements, de novo tubulogenesis and epithelial tubule remodeling. In contrast to the classical epithelial budding and tube extension observed in other organs, a pancreatic branch takes shape as a multi-lumen tubular plexus coordinately extends and remodels into a ramifying, single-lumen ductal system. Moreover, our studies identify a role for EphB signaling in epithelial remodeling during pancreatic branching. Overall, these results illustrate distinct, step-wise cellular mechanisms by which pancreatic epithelium shapes itself to create a functional branching organ.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Alethia
authors.initials: A
authors.lastname: Villasenor
authors.forename: Diana C
authors.initials: DC
authors.lastname: Chong
authors.forename: Mark
authors.initials: M
authors.lastname: Henkemeyer
authors.forename: Ondine
authors.initials: O
authors.lastname: Cleaver
mesh_terms: D000818:Animals; D004848:Epithelium / Q000196:embryology*; D005455:Fluorescent Antibody Technique; D017403:In Situ Hybridization; D051379:Mice; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D010179:Pancreas / Q000196:embryology*; D036183:Receptor, EphB2 / Q000235:genetics / Q000378:metabolism; D036223:Receptor, EphB3 / Q000235:genetics / Q000378:metabolism
chemical_list: D036183:Receptor, EphB2; D036223:Receptor, EphB3