OBJECTIVE: Smooth muscle cell (SMC) differentiation is a critical process during 
cardiovascular formation and development, but the underlying molecular mechanism 
remains unclear.
METHODS AND RESULTS: Here we demonstrated that chromobox protein homolog 3 
(Cbx3) is crucial for SMC differentiation from stem cells and that the 
chromodomain and chromoshadow domain of Cbx3 are responsible for Cbx3-induced 
SMC differentiation. Moreover, we identified that 4 amino acids (165 to 168) 
within the chromoshadow domain of Cbx3 are key elements for Cbx3 interaction 
with Dia-1- and Cbx3-induced SMC differentiation. Mechanistically, we found that 
Cbx3 mediates SMC differentiation through modulating serum response factor (SRF) 
recruitment to the promoters of SMC genes, in which the interaction between Cbx3 
and Dia-1/SRF plays a crucial role in this process. Moreover, our in vivo study 
demonstrated that the misexpression of Cbx3 within neural crest cells of chick 
embryos resulted in the death of chick embryos at early stages because of the 
maldevelopment of branchial arch arteries.
CONCLUSIONS: Our findings suggest that the interaction between Cbx3 and 
Dia-1/SRF is essential for SMC differentiation from stem cells and for the 
development of functional cardiovascular system.