gdf11 is required for pronephros/cloaca development through targeting TGF-β signaling

The kidney is a vital organ responsible for removing toxins, producing urine, and regulating homeostasis. Developmental defects in the kidney lead to various congenital abnormalities that impair renal function. Gdf11, a member of the transforming growth factor β family, is associated with numerous renal abnormalities. In the early developmental stage, the pronephric duct and hindgut open into the cloaca, and Gdf11 shows significant expression in the hindgut of mice. However, the molecular and cellular roles of gdf11 in kidney and cloaca organogenesis remain unclear. Our study revealed that pronephros and cloaca formation were significantly disrupted upon gdf11 deletion or knockdown in zebrafish. Additionally, we found that the TGF-β pathway acts downstream of Gdf11 in promoting pronephros and cloaca development. Treatment with a TGF-β small molecule activator partially rescued the pronephros and cloaca developmental defects observed in gdf11^-/- mutants. In summary, our findings provide strong evidence of a critical link between pronephros/cloaca formation and TGF-β signaling mediated by Gdf11. Our study also provides new insight into diseases related to renal and cloaca development.