Models of the developmental roles of p53. A, A “constitutive” model: p53 and its functionally redundant players, presumably p63 and p73, are constitutively regulating the developmentally essential genes. The loss of p53 is partially compensated for by these redundant players. B, A “passive” model: p53 signaling is activated by stochastic dys-regulation of developmentally essential genes. In the basal condition, p53 is inactive but can be activated in response to developmental stresses. Therefore, p53 signaling plays a “passive” role in development. The stochastic nature of developmental stresses results in the low penetrance of developmental defects in p53 null mice.