Characterizing post-branching nephrogenesis in the neonatal rabbit

Area of Science:

• Developmental Biology
• Nephrology
• Comparative Anatomy

Background:

• Human nephrogenesis concludes before birth, with most nephrons forming during late gestation.
• Preterm infants require postnatal nephrogenesis, and extreme prematurity is linked to lower nephron counts.
• Identifying animal models with postnatal nephrogenesis is crucial for supporting preterm infant kidney development.

Purpose of the Study:

• To investigate whether rabbits undergo post-branching nephrogenesis (PBN) postnatally.
• To characterize the timing and mechanisms of rabbit nephrogenesis.
• To evaluate the rabbit as a model for studying postnatal PBN.

Main Methods:

• Morphological and immunohistological assessments of rabbit kidneys from birth to postnatal day 49.
• Staining with H&E and antibodies for SIX1, SIX2, WT1, ZO-1, and JAG1.
• 3D rendering of the nephrogenic niche and RNAScope for transcript mapping (Six1, Six2, Ret).

Main Results:

• Rabbit SIX2 expression in nephron progenitors (NPC) ceased before SIX1, mirroring the human pattern.
• Active nephrogenesis persisted only until postnatal days 3-5 (PC35-36).
• Morphological analysis revealed evidence of PBN arcades, but not lateral branch nephrogenesis, in postnatal rabbits.

Conclusions:

• The rabbit demonstrates postnatal PBN arcades, albeit for a limited duration (first 5 days of life).
• The rabbit is the first non-primate to express SIX1 in its progenitor population.
• The rabbit serves as a valuable non-primate model for studying arcading in the postnatal nephrogenic niche.