P27(KIP1) IS EXPRESSED TRANSIENTLY IN DEVELOPING MYOTOMES AND ENHANCES MYOGENESIS

Vertebrate skeletal muscle development is characterized by tight coupl ing of muscle differentiation with cell cycle arrest in G(1)/G(0), Key regulators of G(1) progression are the G(1) cyclin-dependent kinases, their positive regulators, the G1 cyclins, and their negative regulat ors, the cyclin-dependent kinase inhibitors (CDIs). Here we show that p27(Kip1) protein, a GI CDI, is expressed in a prominent but transient wave in the developing myotomes of the mouse embryo. We relate its ex pression to expression of MyoD and myogenin proteins, which are determ ination and differentiation class myogenic regulatory factors, respect ively. Functional assays showed that ectopic p27 expression can powerf ully enhance the efficiency of MyoD-initiated muscle differentiation i n cell culture, When considered together with the myotomal expression patterns of p18, p21, and p57, these results suggest a model in which p27 acts as a ''trigger'' CDI while myoblasts are exiting the cell cyc le and initiating differentiation. At later times, when p27 protein ha s been down-regulated, it is proposed that accumulation of p18, p21, a nd p57 maintain the differentiated myocytes in a postmitotic state.