PKD1 and cyst: Interestingly, a fraction of normal-appearing renal tubules around the PC1-negative cysts also hardly expressed PC1 (Fig. 3a, arrowheads), suggesting that intercellular communication between WT and PKD1-null cells may ameliorate the cyst severity of mutant cells, or that the loss of PC1 protein is not sufficient for cyst formation and some other factor may be required, as stipulated by the “three-hit” hypothesis31.