Nephron segmentation involves a concert of genetic and molecular signals that are not fully understood. Through a chemical screen, we discovered that alteration of peroxisome proliferator-activated receptor (PPAR) signaling disrupts nephron segmentation in the zebrafish embryonic kidney (Poureetezadi et al., 2016). Here, we show that the PPAR co-activator ppargc1a directs renal progenitor fate. ppargc1a mutants form a small distal late (DL) segment and an expanded proximal straight tubule (PST) segment. ppargc1a promotes DL fate by regulating the transcription factor tbx2b, and restricts expression of the transcription factor sim1a to inhibit PST fate. Interestingly, sim1a restricts ppargc1a expression to promote the PST, and PST development is fully restored in ppargc1a/sim1a deficient embryos, suggesting Ppargc1a and Sim1a counterbalance each other in an antagonistic fashion to delineate the PST segment boundary during nephrogenesis. Taken together, our data reveal new roles for Ppargc1a during development, which have implications for understanding renal birth defects.
All data generated or analysed during this study are included in the manuscript and supporting files.
- Rebecca A Wingert
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: Zebrafish were maintained in the Center for Zebrafish Research at the University of Notre Dame. All studies were performed with approval of the University of Notre Dame Institutional Animal Care and Use Committee (IACUC), under protocol numbers 13-021 and 16-025.
- Tanya T. Whitfield, University of Sheffield, United Kingdom
© 2018, Chambers et al.
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