Comparison of stem cell therapies for acute kidney injury.

Acute kidney injury (AKI) is the rapid onset of decreased kidney function that ultimately increases mortality and morbidity. Stem cell research is a promising avenue for curative and preventative therapies of kidney injury, however, there are many types of stem cells under investigation. Currently there is no research to compare the value of one stem cell method over another.

Recent advances in elucidating the genetic mechanisms of nephrogenesis using zebrafish.

The kidney is comprised of working units known as nephrons, which are epithelial tubules that contain a series of specialized cell types organized into a precise pattern of functionally distinct segment domains. There is a limited understanding of the genetic mechanisms that establish these discrete nephron cell types during renal development. The zebrafish embryonic kidney serves as a simplified yet conserved vertebrate model to delineate how nephron segments are patterned from renal progenitors.

Flat mount preparation for observation and analysis of zebrafish embryo specimens stained by whole mount in situ hybridization.

The zebrafish embryo is now commonly used for basic and biomedical research to investigate the genetic control of developmental processes and to model congenital abnormalities. During the first day of life, the zebrafish embryo progresses through many developmental stages including fertilization, cleavage, gastrulation, segmentation, and the organogenesis of structures such as the kidney, heart, and central nervous system. The anatomy of a young zebrafish embryo presents several challenges for the visualization and analysis of the tissues involved in many of these events because the embryo develops in association with a round yolk mass.

Zebrafish nephrogenesis is regulated by interactions between retinoic acid, mecom, and Notch signaling.

The zebrafish pronephros provides a conserved model to study kidney development, in particular to delineate the poorly understood processes of how nephron segment pattern and cell type choice are established. Zebrafish nephrons are divided into distinct epithelial regions that include a series of proximal and distal tubule segments, which are comprised of intercalated transporting epithelial cells and multiciliated cells (MCC). Previous studies have shown that retinoic acid (RA) regionalizes the renal progenitor field into proximal and distal domains and that Notch signaling later represses MCC differentiation, but further understanding of these pathways has remained unknown.