Klf15 Is Critical for the Development and Differentiation of Drosophila Nephrocytes.

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 Facto...

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Main Authors: Jessica R Ivy, Maik Drechsler, James H Catterson, Rolf Bodmer, Karen Ocorr, Achim Paululat, Paul S Hartley
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4547745?pdf=render
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spelling doaj-0fb44840db3240c181f73952ba081bc22020-11-24T20:45:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01108e013462010.1371/journal.pone.0134620Klf15 Is Critical for the Development and Differentiation of Drosophila Nephrocytes.Jessica R IvyMaik DrechslerJames H CattersonRolf BodmerKaren OcorrAchim PaululatPaul S HartleyInsect 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.http://europepmc.org/articles/PMC4547745?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Jessica R Ivy
Maik Drechsler
James H Catterson
Rolf Bodmer
Karen Ocorr
Achim Paululat
Paul S Hartley
spellingShingle Jessica R Ivy
Maik Drechsler
James H Catterson
Rolf Bodmer
Karen Ocorr
Achim Paululat
Paul S Hartley
Klf15 Is Critical for the Development and Differentiation of Drosophila Nephrocytes.
PLoS ONE
author_facet Jessica R Ivy
Maik Drechsler
James H Catterson
Rolf Bodmer
Karen Ocorr
Achim Paululat
Paul S Hartley
author_sort Jessica R Ivy
title Klf15 Is Critical for the Development and Differentiation of Drosophila Nephrocytes.
title_short Klf15 Is Critical for the Development and Differentiation of Drosophila Nephrocytes.
title_full Klf15 Is Critical for the Development and Differentiation of Drosophila Nephrocytes.
title_fullStr Klf15 Is Critical for the Development and Differentiation of Drosophila Nephrocytes.
title_full_unstemmed Klf15 Is Critical for the Development and Differentiation of Drosophila Nephrocytes.
title_sort klf15 is critical for the development and differentiation of drosophila nephrocytes.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2015-01-01
description 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.
url http://europepmc.org/articles/PMC4547745?pdf=render
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