Rab11 Regulates Lumen Formation and Morphogenesis in the Developing Pancreas
type: CreativeWork
description: The molecular links between epithelial lumenogenesis and tissue-level morphogenesis in the pancreas remain elusive despite a decade of studies. Here, I show that deletion of Rab11A and Rab11B (Rab11) in the developing pancreatic epithelium (Rab11pancDKO) disrupts both of these processes. The loss of Rab11 in the pancreas results in ~50% neonatal lethality, with the surviving pups failing to thrive. Surviving adult Rab11pancDKO mice are smaller and exhibit defective endocrine function. Loss of Rab11 in the pancreas results in severe morphogenetic defects that are associated with a decrease in endocrine mass during embryonic development. Additionally, Rab11pancDKO pancreata are unable to properly form and connect lumens. Rab11pancDKO cells exhibit defects in coordinating singular apical membrane initiation sites (AMIS) between groups of cells. We show that these phenotypes are due, at least in part, to failures in vesicle trafficking, as apical components remain trapped within Rab11pancDKO cells. These observations suggest Rab11 directly regulates epithelial lumen formation and morphogenesis, which are in turn critical for pancreatic cell fate specification. Furthermore, careful analysis of WT early-stage pancreata reveal the active role of cap cells in microlumen formation. In addition, a literature review of Rho GTPase signaling in the vasculature reinforces many of the fundamental roles of various signaling molecules that also govern pancreas development. These reports link a number of cellular processes in vivo, and presents tantalizing possibilities for decoding pancreatic morphogenesis.
abstract: The molecular links between epithelial lumenogenesis and tissue-level morphogenesis in the pancreas remain elusive despite a decade of studies. Here, I show that deletion of Rab11A and Rab11B (Rab11) in the developing pancreatic epithelium (Rab11pancDKO) disrupts both of these processes. The loss of Rab11 in the pancreas results in ~50% neonatal lethality, with the surviving pups failing to thrive. Surviving adult Rab11pancDKO mice are smaller and exhibit defective endocrine function. Loss of Rab11 in the pancreas results in severe morphogenetic defects that are associated with a decrease in endocrine mass during embryonic development. Additionally, Rab11pancDKO pancreata are unable to properly form and connect lumens. Rab11pancDKO cells exhibit defects in coordinating singular apical membrane initiation sites (AMIS) between groups of cells. We show that these phenotypes are due, at least in part, to failures in vesicle trafficking, as apical components remain trapped within Rab11pancDKO cells. These observations suggest Rab11 directly regulates epithelial lumen formation and morphogenesis, which are in turn critical for pancreatic cell fate specification. Furthermore, careful analysis of WT early-stage pancreata reveal the active role of cap cells in microlumen formation. In addition, a literature review of Rho GTPase signaling in the vasculature reinforces many of the fundamental roles of various signaling molecules that also govern pancreas development. These reports link a number of cellular processes in vivo, and presents tantalizing possibilities for decoding pancreatic morphogenesis.
author: Barlow, Haley Rose
language: en
keywords: Pancreas, rab GTP-Binding Proteins
date published: 2025-01-02T21:57:59Z
date modified: 2026-07-24T05:52:13Z
provider: University of Texas Southwestern Medical Center
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Texas Southwestern Medical Center

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2152.5/10451