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© The Rockefeller University Press, 0021-9525/1998//403 $5.00
The Journal of Cell Biology, Volume 143, Number 2, , 1998 403-413

Regular Articles

CDO, A Robo-related Cell Surface Protein that Mediates Myogenic Differentiation



Jong-Sun Kang*, Philip J. Mulieri*, Cary Miller§, David A. Sassoon§, and Robert S. Krauss*

* Department of Biochemistry and § Brookdale Center for Molecular and Developmental Biology, Mount Sinai School of Medicine, New York, New York 10029

CDO, a member of the Ig/fibronectin type III repeat subfamily of transmembrane proteins that includes the axon guidance receptor Robo, was identified by virtue of its down-regulation by the ras oncogene. We report here that one prominent site of cdo mRNA expression during murine embryogenesis is the early myogenic compartment (newly formed somites, dermomyotome and myotome). CDO is expressed in proliferating and differentiating C2C12 myoblasts and in myoblast lines derived by treating 10T1/2 fibroblasts with 5-azacytidine, but not in parental 10T1/2 cells. Overexpression of CDO in C2C12 cells accelerates differentiation, while expression of secreted soluble extracellular regions of CDO inhibits this process. Oncogenic Ras is known to block differentiation of C2C12 cells via downregulation of MyoD. Reexpression of CDO in C2C12/Ras cells induces MyoD; conversely, MyoD induces CDO. Reexpression of either CDO or MyoD rescues differentiation of C2C12/Ras cells without altering anchorage-independent growth or morphological transformation. CDO and MyoD are therefore involved in a positive feedback loop that is central to the inverse relationship between cell differentiation and transformation. It is proposed that CDO mediates, at least in part, the effects of cell–cell interactions between muscle precursors that are critical in myogenesis.

Key Words: myogenesis • MyoD • CDO • Ras • cell differentiation

The authors dedicate this paper to the memory of Eugenia Spanopoulou.

Address all correspondence to Robert S. Krauss, Department of Biochemistry, Box 1020, Mount Sinai School of Medicine, New York, NY 10029. Tel.: (212) 241-2177. Fax: (212) 996-7214. E-mail: rkrauss{at}smtplink.mssm.edu

1. Abbreviations used in this paper: AP, alkaline phosphatase; bHLH, basic helix-loop-helix; CM, conditioned media; DM differentiation medium; FNIII, fibronectin type III; GM, growth medium; MEF-2, myocyte enhancer binding factor-2; MHC, myosin heavy chain; TnT, troponin T.


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