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Abstract: FR-PO392

Evidence for Post-Branching Nephrogenesis and Novel Ureteric Bud/Nephron Progenitor Interaction in the Postnatal Rabbit

Session Information

Category: Development‚ Stem Cells‚ and Regenerative Medicine

  • 500 Development‚ Stem Cells‚ and Regenerative Medicine

Authors

  • Schuh, Meredith Posner, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Yarlagadda, Sunitha, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Alkhudairy, Lyan, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Kopan, Raphael, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
Background

While all vertebrates undergo branching nephrogenesis, humans proceed in two additional post-branching nephrogenesis (PBN) periods: arcading and lateral branch nephrogenesis (LBN). This process is completed at 34-36 weeks gestation, with 60% of nephrons forming in the third trimester. Infants born before 30 weeks undergo nephrogenesis for no more than 40 days postnatally, resulting in low nephron endowment and increased risk for chronic kidney disease (CKD) later in life. Identifying a model that simulates human postnatal nephrogenesis is critical in order to reduce risk of CKD in this population. The rabbit continues nephrogenesis postnatally but whether it has PBN has not been determined. Without this knowledge, its utility as a model of preterm human remains unknown.

Methods

To address this, we performed morphologic assessments of rabbit nephrogenesis from post conceptual day (PC) 31 (birth) to PC49 using H&E and immunofluorescence to localize SIX1, SIX2, WT1, ZO-1, and JAG1 in the postnatal period. We performed 3D rendering of the nephrogenic niche to assess for PBN, and applied RNAScope to localize the nephrogenic niche by expression of Six1 (nephron progenitors, NPC) and Ret (ureteric bud (UB) tip) transcripts.

Results

Using molecular markers, SIX1 and SIX2+ were identified in the NPC throughout nephrogenesis. 3D morphologic assessments identified an elongated tubule with attached glomeruli extending below the UB tip, consistent with PBN arcades. Above these arcades, the UB tip contained a horn-like protrusion interacting with an immature WT1+ NPC population (fig 1). The Ret+ UB horns were present until PC38, while the arcades were Cdh1+/Ret-.

Conclusion

We conclude that the rabbit shows morphologic and molecular evidence of PBN continuing postnatally. Furthermore, we identified a novel UB/NPC interaction during the arcading period.

Figure 1: Arcades visualized in Posnatal Rabbit

Funding

  • Other NIH Support