Abstract:
:It is widely acknowledged that cultured myoblasts can not differentiate at very low density. Here we analyzed the mechanism through which cell density influences myogenic differentiation in vitro. By comparing the behavior of C2C12 myoblasts at opposite cell densities, we found that, when cells are sparse, failure to undergo terminal differentiation is independent from cell cycle control and reflects the lack of p27Kip1 and MyoD in proliferating myoblasts. We show that inhibition of p27Kip1 expression impairs C2C12 cell differentiation at high density, while exogenous p27Kip1 allows low-density cultured C2C12 cells to enter the differentiative program by regulating MyoD levels in undifferentiated myoblasts. We also demonstrate that the early induction of p27Kip1 is a critical step of the N-cadherin-dependent signaling involved in myogenesis. Overall, our data support an active role of p27Kip1 in the decision of myoblasts to commit to terminal differentiation, distinct from the regulation of cell proliferation, and identify a pathway that, reasonably, operates in vivo during myogenesis and might be part of the phenomenon known as "community effect".
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Messina G,Blasi C,La Rocca SA,Pompili M,Calconi A,Grossi Mdoi
10.1091/mbc.e04-07-0612keywords:
subject
Has Abstractpub_date
2005-03-01 00:00:00pages
1469-80issue
3eissn
1059-1524issn
1939-4586pii
E04-07-0612journal_volume
16pub_type
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