The molecular and cellular anatomy of a fetal programming defect - the impact of low protein diet on the developing kidney.
Kieran M ShortGiovane G TorteloteLynelle K JonesFabiola DinizFrancesca Edgington-GiordanoLouise A Cullen-McEwenJan SchroederAshley SpencerAndrew KeniryMohammad Mahfuz ChowdhuryJohn F BertramMarnie E BlewittIan M SmythSamir S El-DahrPublished in: bioRxiv : the preprint server for biology (2023)
While a mother's diet and behavior can negatively impact the number of nephrons in the kidneys of her offspring, the root cellular and molecular drivers of these deficits have not been rigorously explored. In this study we use advanced imaging and gene expression analysis in mouse models to define how a maternal low protein diet, analogous to that of impoverished communities, results in reduced nephron endowment. We find that low protein diet has pleiotropic effects on metabolism and the normal programs of gene expression. These profoundly impact the process of branching morphogenesis necessary to establish niches for nephron generation and change cell behaviors which regulate how and when nephron progenitor cells commit to differentiation.