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* Ludwig Institute for Cancer Research and Withdrawal from the cell cycle is an essential
aspect of vertebrate muscle differentiation and requires
the retinoblastoma (Rb) protein that inhibits expression of genes needed for cell cycle entry. It was shown
recently that cultured myotubes derived from the
Rb Department of Biochemistry and Molecular Biology, University College London,
London W1P 8BT, United Kingdom; and § Division of Biological Sciences, Lancaster University, Lancaster LA1 4YQ, United
Kingdom
/mouse reenter the cell cycle after serum stimulation (Schneider, J.W., W. Gu, L. Zhu, V. Mahdavi, and
B. Nadal-Ginard. 1994. Science (Wash. DC). 264:1467-
1471). In contrast with other vertebrates, adult urodele
amphibians such as the newt can regenerate their limbs,
a process involving cell cycle reentry and local reversal of differentiation. Here we show that myotubes formed
in culture from newt limb cells are refractory to several
growth factors, but they undergo S phase after serum
stimulation and accumulate 4N nuclei. This response to
serum is inhibited by contact with mononucleate cells.
Despite the phenotypic parallel with Rb/ mouse myotubes, Rb is expressed in the newt myotubes, and its phosphorylation via cyclin-dependent kinase 4/6 is required for cell cycle reentry. Thus, the postmitotic arrest of urodele myotubes, although intact in certain respects, can be undermined by a pathway that is inactive
in other vertebrates. This may be important for the regenerative ability of these animals.
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