title: 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 (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.
authors.affiliation: Stowers Institute for Medical Research, Kansas City, United States.
authors.forename: Hanh
authors.initials: H
authors.lastname: Thi-Kim Vu
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Jochen C
authors.initials: JC
authors.lastname: Rink
authors.affiliation: Stowers Institute for Medical Research, Kansas City, United States.
authors.forename: Sean A
authors.initials: SA
authors.lastname: McKinney
authors.affiliation: Stowers Institute for Medical Research, Kansas City, United States.
authors.forename: Melainia
authors.initials: M
authors.lastname: McClain
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Naharajan
authors.initials: N
authors.lastname: Lakshmanaperumal
authors.affiliation: Stowers Institute for Medical Research, Kansas City, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Alexander
authors.affiliation: Stowers Institute for Medical Research, Kansas City, United States.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sánchez Alvarado
mesh_terms: D000818:Animals; D001826:Body Fluids / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D003560:Cysts / Q000473:pathology*; D004195:Disease Models, Animal; D055785:Gene Knockdown Techniques; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000473:pathology* / Q000503:physiopathology*; D010932:Planarians / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D013234:Stem Cells / Q000502:physiology*
keywords: cystic kidney disease; developmental biology; excretory system; planaria; stem cells