Drosophila Bteb2, a Kruppel-like transcription factor, specifies and maintains adult pericardial nephrocytes

Authors: Ivy, J.R., Catterson, J.H. and Hartley, P.

Start date: 10 July 2012

Drosophila Bteb2 (dBteb2) is a Kruppel-like transcription factor (KLF) with no known function but which has mammalian orthologs that regulate cardiac hypertrophy and kidney fibrosis. dBteb2 expression initiates during embryogenesis and is sustained in the adult heart, which comprises contractile cardiomyocytes and pericardial nephrocytes (PNs), cells that represent important models of mammalian cardiac and kidney podocyte function. In this work we explored the role of dBteb2 in Drosophila using flies carrying a P-element insertion in the dBteb2 gene and RNAi-mediated silencing of dBteb2 during development and adulthood, in heart cells and nephrocytes. We found that the flies with the P-element insertion had negligible dBteb2 expression and that this was associated with the absence of PNs in adults and a slow heart rate. RNAi-mediated silencing of dBteb2 using two independent RNAi lines under the control of the Hand driver also prevented PN development. Temporal and regional control of gene expression (TARGET) was used to silence dBteb2 in the adult heart and PNs and this led to a profound impact on PN morphology and endocytic function but not viability. These data establish that dBteb2 regulates the development of pericardial nephrocytes in Drosophila. Secondly, sustained expression of dBteb2 is required to maintain the functional integrity of the adult pericardial nephrocyte lineage. We propose that the dBteb2 transcriptional pathway represents an important model of KLF activity within mammalian kidney podocytes.

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