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Kidney Week

Abstract: PO0620

Autonomous Calcium Signaling in Human and Zebrafish Podocytes Controls Kidney Filtration Barrier Morphogenesis

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 500 Development, Stem Cells, and Regenerative Medicine


  • Djenoune, Lydia, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Schenk, Heiko Joachim, Mount Desert Island Biological Laboratory, Salsbury Cove, Maine, United States
  • Hegermann, Jan, Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany
  • Little, Melissa H., Murdoch Childrens Research Institute, Parkville, Victoria, Australia
  • Drummond, Iain A., Mount Desert Island Biological Laboratory, Salsbury Cove, Maine, United States

Mutations in nephrotic syndrome genes that lead to elevated cytoplasmic calcium in podocytes cause disruption of filtration barrier function and nephrotic syndrome. Whether calcium signaling plays a role in the initial formation of the filtration barrier is not known. Here we show that calcium signaling is active during podocyte differentiation, occurs independently of neighboring cell types, and is required for foot process and slit diaphragm formation.


The calcium biosensor GCaMP6s was expressed in zebrafish podocytes during larval development using a podocin:Gal4 x UAS:GCAMPs transgene cross to evaluate calcium signaling during development. Calcium signals in differentiating podocytes in human kidney organoids were detected using Fluo-4. Filtration barrier formation in zebrafish was evaluated by electron microscopy.


Immature zebrafish podocytes generated calcium transients that correlated with interactions with forming glomerular capillaries. Calcium transients persisted until 4 dpf and were absent after glomerular barrier formation was complete. Similar calcium transients were detected in maturing human organoid glomeruli suggesting a conserved mechanism. In both models, inhibitors of SERCA or IP3 receptor calcium-release channels blocked calcium transients in podocytes, while lanthanum was ineffective, indicating the source of calcium is podocyte intracellular stores. Calcium transients were not affected by deficiencies in heartbeat, endothelium or endoderm, and persisted in isolated glomeruli, suggesting that they were generated cell autonomously. Inhibition of phospholipase C gamma 1 (PLCg1), but not Nephrin or phospholipase C epsilon1 (PLCe1), expression lead to a significant decrease in calcium activity. Finally, blocking calcium release impacted glomerular shape and podocyte foot process formation, supporting the critical role of calcium signaling in glomerular morphogenesis.


Our results establish cell autonomous calcium signaling as a prominent and conserved feature of podocyte differentiation and demonstrate the requirement for intracellular calcium elevations for podocyte foot process formation.


  • NIDDK Support