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Elife. 2015 Jun 9;4. doi: 10.7554/eLife.07405.

Stem cells and fluid flow drive cyst formation in an invertebrate excretory organ.

Author information

1
Stowers Institute for Medical Research, Kansas City, United States.
2
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.

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 (Caenorhabditis elegans and Drosophila 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.

KEYWORDS:

cystic kidney disease; developmental biology; excretory system; planaria; stem cells

PMID:
26057828
PMCID:
PMC4500094
DOI:
10.7554/eLife.07405
[Indexed for MEDLINE]
Free PMC Article

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