ppargc1a controls nephron segmentation during zebrafish embryonic kidney ontogeny
Joseph M Chambers,
Shahram Jevin Poureetezadi,
Amanda Addiego,
Manuela Lahne,
Rebecca A Wingert
Affiliations
Joseph M Chambers
Department of Biological Sciences, University of Notre Dame, Indiana, United States; Center for Stem Cells and Regenerative Medicine, University of Notre Dame, Indiana, United States; Center for Zebrafish Research, University of Notre Dame, Indiana, United States
Shahram Jevin Poureetezadi
Department of Biological Sciences, University of Notre Dame, Indiana, United States; Center for Stem Cells and Regenerative Medicine, University of Notre Dame, Indiana, United States; Center for Zebrafish Research, University of Notre Dame, Indiana, United States
Amanda Addiego
Department of Biological Sciences, University of Notre Dame, Indiana, United States; Center for Stem Cells and Regenerative Medicine, University of Notre Dame, Indiana, United States; Center for Zebrafish Research, University of Notre Dame, Indiana, United States
Manuela Lahne
Department of Biological Sciences, University of Notre Dame, Indiana, United States; Center for Stem Cells and Regenerative Medicine, University of Notre Dame, Indiana, United States; Center for Zebrafish Research, University of Notre Dame, Indiana, United States
Department of Biological Sciences, University of Notre Dame, Indiana, United States; Center for Stem Cells and Regenerative Medicine, University of Notre Dame, Indiana, United States; Center for Zebrafish Research, University of Notre Dame, Indiana, United States
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.
