Circadian Clock Regulation of Developmental Time in the Kidney

Abstract

We report the emergence of an endogenous circadian clock that regulates organogenesis in mouse fetal kidney. We detect circadian rhythms both in vivo with transcriptional profiling and ex vivo by bioluminescence. High-resolution structural analysis of embryonic explants reveals that global or local clock disruption results in defects that resemble human congenital abnormalities of the kidney. The onset of fetal rhythms strongly correlates with the timing of a distinct transition in branching and growth rates during a gestational window of high fetal growth demands. Defects in clock mutants typically have been attributed to accelerated aging; however, our study establishes a role for the fetal circadian clock as a developmental timer that regulates the pathways that control organogenesis, branching rate, and nephron number and thus plays a fundamental role in kidney development.

Keywords: CAKUT; branching morphogenesis; circadian clock; developmental programming; kidney development; organogenesis.