Elucidating the Role of Apolipoprotein L1 in Zebrafish Pronephros Development

Background: Chronic kidney disease (CKD) is a significant burden in America. Apolipoprotein L1 (APOL1) mutations have been linked to an increased risk of kidney disease and failure in African and African American populations. APOL1 is highly expressed in various tissues, including the kidney, but the function of APOL1 in the kidney is unknown. Methods: In this study, we utilized the zebrafish to create apol1 loss-of-function models to study its roles in renal development, specifically nephrogenesis. The zebrafish is uniquely suited for this study due to its high conservation with the mammalian kidney and being one of the few organisms with apol1 in its genome. Whole-mount in situ hybridization, immunofluorescence, HCR technology, and pharmacological treatments were employed to examine transcripts and cell dynamics of renal progenitors. Results: This study revealed that the loss of apol1 reduced the expression of podocyte regulator wt1a and lineage markers wt1b and nephrin. Furthermore, loss of apol1 dysregulated the interrenal marker nr5a1a. These findings suggest that apol1 is crucial for cell fate choice between the podocyte and interrenal lineages. Ongoing investigations aim to discern the interplay between apol1, retinoic acid (RA), and Notch signaling in renal development. Conclusion: Using the zebrafish to investigate the role of apol1 in the development of podocyte formation, indicated that apol1 is necessary in maintaining podocyte cell fate through regulation of the Notch signaling pathway during podocyte differentiation. Further research is needed to determine the role of RA signaling in apol1-mediated podocyte cell fate and maturity. Funding: Private Foundation Support