The zebrafish (Danio rerio) has emerged as a powerful vertebrate model for studying kidney development and regeneration due to its remarkable capacity to regenerate nephron structures following injury. Unlike mammals, zebrafish retain the ability to regenerate functional nephrons throughout life, making them an ideal system for dissecting the cellular and molecular pathways underlying renal repair.

During development, zebrafish form a pronephros composed of two nephrons, which later transitions into a mesonephros containing dozens of nephrons similar in structure to those found in mammals. Importantly, zebrafish kidneys can regenerate nephrons de novo following damage via activation of renal progenitor cells. These progenitors are capable of proliferating, differentiating, and integrating into the existing kidney architecture, restoring its function.

Key signaling pathways—including Wnt, Notch, retinoic acid, and FGF—have been implicated in guiding nephrogenesis and regenerative processes. The transparent nature of zebrafish embryos and the availability of powerful genetic tools allow for in vivo imaging and functional analysis of these pathways during both development and regeneration.

Understanding how zebrafish achieve such robust kidney repair provides valuable insights into the limited regenerative capacity of the human kidney. By uncovering conserved and divergent mechanisms, this research holds promise for developing regenerative therapies aimed at treating acute kidney injury and chronic kidney disease in humans.

This Research Topic welcomes contributions that investigate cellular dynamics, lineage specification, genetic regulation, and intercellular signaling pathways underpinning zebrafish kidney development and regeneration., with the aim of advancing regenerative medicine and kidney biology. The articles may cover, but not limited to, the following topics:

• Characterization of Renal Progenitor Cells: Identify and track renal progenitor cell populations involved in nephron regeneration post-injury.

• Signaling Pathways in Regeneration: Investigate the roles of Wnt, Notch, BMP, FGF, and retinoic acid pathways in guiding nephron repair.

• Comparative Transcriptomics: Analyze gene expression profiles during development and post-injury regeneration to identify key regulatory genes.

• Cellular Plasticity: Investigate whether differentiated renal cells dedifferentiate and contribute to regeneration following injury.

• Temporal Dynamics of Regeneration: Analyze time-resolved cellular events and gene expression changes during injury response and recovery.

• Developmental Pathway Reactivation: Identify developmental pathways (e.g., Wnt, BMP, Notch) reactivated during regeneration and their downstream cellular effects.

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Regenerative Mechanisms in Zebrafish Kidney Development and Injury Response