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Abstract: TH-PO0542

Convergence and Divergence of Mammalian Postbranching Nephrogenesis

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 600 Development, Stem Cells, and Regenerative Medicine

Authors

  • Nakum, Cimran, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Indugula, Shalini, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Yarlagadda, Sunitha, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Bull, Brandi C, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Roy, Debarun, The University of Texas at San Antonio, San Antonio, Texas, United States
  • Hermann, Brian P, The University of Texas at San Antonio, San Antonio, Texas, United States
  • Schuh, Meredith Posner, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
Background

Human nephrogenesis ends prior to birth in term infants (34-36 week gestation), with most (60%) nephrons being formed during late gestation in two post-branching nephrogenesis (PBN) periods: arcading and lateral branch nephrogenesis (LBN). We previously demonstrated the rabbit as a model of arcading and the rhesus of lateral branch nephrogenesis. In this study, we sought to determine if the marmoset and rat underwent arcading and/or LBN.

Methods

Comparative developmental analyses were performed before nephrogenesis cessation in the rat, rabbit, marmoset, and rhesus. We performed 3D rendering of the nephrogenic niche to assess for PBN. Immunofluorescence was performed to evaluate markers of nephrogenesis, including SIX2, WT1, and RET.

Results

3D morphologic assessments of the marmoset and rat cortical nephrons identified elongated tubules with attached glomeruli extending below the ureteric bud (UB) tip, consistent with PBN arcades, but not with lateral branch nephrogenesis. The rat, rabbit, and marmoset all demonstrate arcading nephrogenesis with similar expression of nephrogenic markers. In all, the UB tip above these arcades contained a horn-like protrusion interacting with an immature SIX2 and NPC population.

Conclusion

Arcading and LBN are both forms of post-branching nephrogenesis and critical steps for human nephron formation. Unlike the rhesus, the marmoset does not show evidence of LBN, even in late gestation. While LBN is unique to old world primates, the induction of a nephron without branching of the UB tip is conserved in both arcading and LBN and demonstrated among the species described here.

Funding

  • NIDDK Support

Digital Object Identifier (DOI)