Feedback regulation of steady-state epithelial turnover and organ size

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Abstract/Contents

Abstract
Continual cell turnover is crucial for the long‐term maintenance of healthy organs, but to avoid pathological consequences, new cells must be produced at the precise rate that old cells are lost. Here we identify the signaling basis of feedback inhibition that equalizes cell production and loss during stem cell‐driven turnover of the Drosophila intestinal epithelium. E‐cadherin at the cortex of mature enterocytes inhibits EGF‐dependent stem cell divisions by repressing the EGF maturation factor rhomboid. Single, apoptotic enterocytes disrupt this inhibitory relay by degrading E‐cadherin, which de‐ represses rhomboid to activate EGFR and promote divisions of nearby stem cells. Ectopic loss of E‐cadherin in non‐apoptotic cells upregulates rhomboid, causing EGFR hyperactivation and excessive divisions. In contrast, blocking apoptosis precludes EGFR activation and slows down divisions to keep total cells constant. Thus, stem cell divisions require enterocyte apoptosis to relieve proliferative inhibition, ensuring equal rates of cell production and loss.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2017
Issuance monographic
Language English

Creators/Contributors

Associated with Liang, Jackson
Associated with Stanford University, Department of Molecular and Cellular Physiology.
Primary advisor O'Brien, Lucy
Thesis advisor O'Brien, Lucy
Thesis advisor Axelrod, Jeffrey (Jeffrey David)
Thesis advisor Nelson, William
Thesis advisor Nusse, Roel, 1950-
Advisor Axelrod, Jeffrey (Jeffrey David)
Advisor Nelson, William
Advisor Nusse, Roel, 1950-

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Jackson Liang.
Note Submitted to the Department of Molecular and Cellular Physiology.
Thesis Thesis (Ph.D.)--Stanford University, 2017.
Location electronic resource

Access conditions

Copyright
© 2017 by Jackson Liang
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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