Spatial and temporal expression patterns of the cyclin-dependent kinase (CDK) inhibitors p27^Kip1 and p57^Kip2 during mouse development

Abstract 

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 are 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.