QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 16, Issue 3, 1469-1480, March 2005

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E04-07-0612v1 16/3/1469    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Messina, G. Articles by Grossi, M. Search for Related Content PubMed PubMed Citation Articles by Messina, G. Articles by Grossi, M.

p27^Kip1 Acts Downstream of N-Cadherin-mediated Cell Adhesion to Promote Myogenesis beyond Cell Cycle Regulation

Istituto Pasteur-Fondazione Cenci-Bolognetti, Dipartimento di Biologia Cellulare e dello Sviluppo, Università di Roma "La Sapienza", 00185 Roma, Italy

Submitted July 21, 2004; Revised December 2, 2004; Accepted December 23, 2004
Monitoring Editor: Richard Assoian

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 p27^Kip1 and MyoD in proliferating myoblasts. We show that inhibition of p27^Kip1 expression impairs C2C12 cell differentiation at high density, while exogenous p27^Kip1 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 p27^Kip1 is a critical step of the N-cadherin-dependent signaling involved in myogenesis. Overall, our data support an active role of p27^Kip1 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".

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

^* Present address: Department of Immunology and Pathology, Institute of Animal Health, Pirbright Surrey, GU24 ONF United Kingdom.

Address correspondence to: Milena Grossi (milena.grossi{at}uniroma1.it).

This article has been cited by other articles:

				E. Susaki, K. Nakayama, L. Yamasaki, and K. I. Nakayama Common and specific roles of the related CDK inhibitors p27 and p57 revealed by a knock-in mouse model PNAS, March 31, 2009; 106(13): 5192 - 5197. [Abstract] [Full Text] [PDF]

				J. Kucharczak, S. Charrasse, F. Comunale, J. Zappulla, B. Robert, I. Teulon-Navarro, A. Pelegrin, and C. Gauthier-Rouviere R-Cadherin Expression Inhibits Myogenesis and Induces Myoblast Transformation via Rac1 GTPase Cancer Res., August 15, 2008; 68(16): 6559 - 6568. [Abstract] [Full Text] [PDF]

				D. Theard, M. A. Raspe, D. Kalicharan, D. Hoekstra, and S. C.D. van IJzendoorn Formation of E-Cadherin/{beta}-Catenin-based Adherens Junctions in Hepatocytes Requires Serine-10 in p27(Kip1) Mol. Biol. Cell, April 1, 2008; 19(4): 1605 - 1613. [Abstract] [Full Text] [PDF]

				D. Pajalunga, A. Mazzola, A. M. Salzano, M. G. Biferi, G. De Luca, and M. Crescenzi Critical requirement for cell cycle inhibitors in sustaining nonproliferative states J. Cell Biol., March 12, 2007; 176(6): 807 - 818. [Abstract] [Full Text] [PDF]

				S. J. Lees, C. R. Rathbone, and F. W. Booth Age-associated decrease in muscle precursor cell differentiation Am J Physiol Cell Physiol, February 1, 2006; 290(2): C609 - C615. [Abstract] [Full Text] [PDF]