Spatial and temporal expression patterns of the cyclin-dependent kinase (CDK) inhibitors p27Kip1 and p57Kip2 during mouse development

The cyclin-dependent kinase (CDK) inhibitors p27(Kip1) and p57(Kip2) are thought to regulate progression of the cell cycle. We have previously shown that the phenotypes of p27(-/-) mice are substantially different from those of p57(-/-) mice, suggesting that spatial and temporal expression patterns of p27(Kip1) and p57(Kip2) might be distinct. In this study, the roles of p27(Kip1) and p57(Kip2) in development were examined by characterizing their expression patterns during mouse embryogenesis by immunohistochemical analysis. Whereas certain organs and tissues (brain, lens, ganglion, lung, heart, liver, skin and kidney) expressed both proteins, others expressed only p27(Kip1) (thymus, spleen, retina, testis and ovary) or only p57(Kip2) (gut, palate, pancreas, cartilage and skeletal muscle). In addition, some organs expressed both p27(Kip1) and p57(Kip2) but showed mutually exclusive patterns of distribution among tissues. Thus, in the adrenal gland, p57(Kip2) was expressed in the cortex but not in the medulla, whereas p27(Kip1) was expressed in the medulla but not in the cortex. Whereas the expression of p57(Kip2) in most tissues was restricted to embryogenesis, expression of p27(Kip1) in, many tissues was maintained in adult animals. Double-label immunofluorescence staining with either anti-p27(Kip1) Or anti-p57(Kip2) and anti-BrdU revealed that the expression of p27(Kip1) and p57(Kip2) was inversely correlated with cell proliferation, suggesting that p27(Kip1) and p57(Kip2) expressed exclusively in postmitotic cells. These complex spatial and temporal patterns of expression are consistent with the phenotypes of mice deficient in p27(Kip1) or p57(Kip2) and they suggest that these proteins might play important roles in tissue development.