title: Klf15 Is Critical for the Development and Differentiation of Drosophila Nephrocytes.
abstract: Insect nephrocytes are highly endocytic scavenger cells that represent the only invertebrate model for the study of human kidney podocytes. Despite their importance, nephrocyte development is largely uncharacterised. This work tested whether the insect ortholog of mammalian Kidney Krüppel-Like Factor (Klf15), a transcription factor required for mammalian podocyte differentiation, was required for insect nephrocyte development. It was found that expression of Drosophila Klf15 (dKlf15, previously known as Bteb2) was restricted to the only two nephrocyte populations in Drosophila, the garland cells and pericardial nephrocytes. Loss of dKlf15 function led to attrition of both nephrocyte populations and sensitised larvae to the xenotoxin silver nitrate. Although pericardial nephrocytes in dKlf15 loss of function mutants were specified during embryogenesis, they failed to express the slit diaphragm gene sticks and stones and did not form slit diaphragms. Conditional silencing of dKlf15 in adults led to reduced surface expression of the endocytic receptor Amnionless and loss of in vivo scavenger function. Over-expression of dKlf15 increased nephrocyte numbers and rescued age-dependent decline in nephrocyte function. The data place dKlf15 upstream of sns and Amnionless in a nephrocyte-restricted differentiation pathway and suggest dKlf15 expression is both necessary and sufficient to sustain nephrocyte differentiation. These findings explain the physiological relevance of dKlf15 in Drosophila and imply that the role of KLF15 in human podocytes is evolutionarily conserved.
authors: University of Edinburgh / British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, United Kingdom.
authors: Jessica R
authors: JR
authors: Ivy
authors: Department of Zoology & Developmental Biology, University of Osnabrück, Barbarastr. 11, D-49069 Osnabrück, Germany.
authors: Maik
authors: M
authors: Drechsler
authors: University of Edinburgh / British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, United Kingdom.
authors: James H
authors: JH
authors: Catterson
authors: Neuroscience and Aging Research Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, United States of America.
authors: Rolf
authors: R
authors: Bodmer
authors: Neuroscience and Aging Research Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, United States of America.
authors: Karen
authors: K
authors: Ocorr
authors: Department of Zoology & Developmental Biology, University of Osnabrück, Barbarastr. 11, D-49069 Osnabrück, Germany.
authors: Achim
authors: A
authors: Paululat
authors: Department of Life and Environmental Science, University of Bournemouth, Talbot Campus, Poole, Dorset BH12 5BB, United Kingdom.
authors: Paul S
authors: PS
authors: Hartley
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology / Q000254:growth & development*; D051741:Kruppel-Like Transcription Factors / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; C000607593:Klf15 protein, Drosophila; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors