Feedback regulation of steady-state epithelial turnover and organ size
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 |
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Form | electronic; electronic resource; remote |
Extent | 1 online resource. |
Publication date | 2017 |
Issuance | monographic |
Language | English |
Creators/Contributors
Associated with | Liang, Jackson | |
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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 |
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Bibliographic information
Statement of responsibility | Jackson Liang. |
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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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