E2, Brute? Unveiling an unexpected role of estrogen signaling in nephrogenesis during embryonic zebrafish kidney development

Recent years have heralded many exciting advancements in our knowledge about kidney development. In particular, there has been tremendous progress in identifying genes and signaling pathways that pattern renal functional units - a process known as nephron segmentation. An intriguing potential regulator of this process, 17β-estradiol (E2), was implicated previously by a high-throughput screen that examined the effects of known bioactive molecules on nephrogenesis. Now, a detailed study has shown that exogenous E2 or exposure to several xenoestrogens has significant effects on nephron distal tubule establishment during development of the zebrafish pronephros, or embryonic kidney. Attenuation of estrogen receptor 2b (Esr2b) activity by pharmacological antagonism or genetic knockdown revealed that E2/Esr2b signaling is necessary for normal distal segment pattern by regulating the expression of Iroquois transcription factors. These findings demonstrate that estrogen signaling influences renal stem cell development during the process of vertebrate nephron segmentation and may have important ramifications for understanding congenital birth defects and kidney diseases.