Stem cells and fluid flow drive cyst formation in an invertebrate excretory organ
Abstract
Cystic kidney diseases (CKDs) affect millions of people worldwide. The defining pathological features are fluid-filled cysts developing from nephric tubules due to defective flow sensing, cell proliferation and differentiation. The underlying molecular mechanisms, however, remain poorly understood, and the derived excretory systems of established invertebrate models (C. elegans and D. melanogaster) are unsuitable to model CKDs. Systematic structure/function comparisons revealed that the combination of ultrafiltration and flow-associated filtrate modification that is central to CKD etiology is remarkably conserved between the planarian excretory system and the vertebrate nephron. Consistently, both RNA-mediated genetic interference (RNAi) of planarian orthologues of human CKD genes and inhibition of tubule flow led to tubular cystogenesis that share many features with vertebrate CKDs, suggesting deep mechanistic conservation. Our results demonstrate a common evolutionary origin of animal excretory systems and establish planarians as a novel and experimentally accessible invertebrate model for the study of human kidney pathologies.
Article and author information
Author details
Reviewing Editor
- Yukiko M Yamashita, University of Michigan, United States
Version history
- Received: March 10, 2015
- Accepted: June 9, 2015
- Accepted Manuscript published: June 9, 2015 (version 1)
- Version of Record published: July 14, 2015 (version 2)
Copyright
© 2015, Thi-Kim Vu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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