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.

Krüppel–Like Factor 15 Mediates Glucocorticoid-Induced Restoration of Podocyte Differentiation Markers

“…35 Recent studies in Drosophila revealed that Klf15 is critical for nephrocyte development and differentiation. 36 Combined with our previous work, 15 we show here that the KLF15 is required for DEX-induced restoration of podocyte differentiation markers (i.e., expression of nephrin and synaptopodin and actin stress fiber formation). Podocin-Cre Klf15 flox/flox mice only exhibited approximately 50% knockdown in KLF15 expression, which likely attributed to less severe podocyte injury in the proteinuric murine models compared with the global Klf15 2/2 mice.…”

SPARCling Study of a Drosophila Cardiomyopathy

“…8 In the current issue of the Journal , these groups extend their investigations to address how nephrocytes influence cardiomyocytes. 9 Using dKlf15 NN/NN mutants, that harbor a piggyBac P-element insertion within the coding region of dKlf15 and lack pericardial nephrocytes, the authors observed bradycardia, prolongation of the diastolic period, and increased systolic and diastolic dimensions.…”

Partner-specific induction ofSpodoptera frugiperdaimmune genes in response to the entomopathogenic nematobacterial complexSteinernema carpocapsae-Xenorhabdus nematophila

“…The signaling ones encoded 3 homologs of the transcription factor Krüppel (Kr) (Fig 1C). In D. melanogaster , Kr and Kr homologs are involved in several developmental processes such as embryo patterning (71), organogenesis (72–74), and cell differentiation (75). More specifically in the hemocytes, Kr has been shown to take part in hemocytes’ differentiation and/or activation (76), a crucial step for the induction of cellular immune responses.…”