Homeobox Genes Play an Important Role in Smooth Muscle Cell Development

The mechanisms of regulation of vascular smooth muscle cell (SMC) differentiation during embryonic development are not well-understood. In this study, we examine the role of the mesodermal homeobox protein, Meox1, in promoting SMC differentiation during vascular development. In situ hybridization showed Meox1 expression in embryonic mesoderm and the truncus arteriosis which contribute to development of smooth muscle. Meox1 expression was rapidly and transiently induced following retinoic acid (RA)-induced differentiation of A404 SMC progenitor cells and in an RA-embryonic stem cell–embryoid body model (ESC-EB) of SMC differentiation. Meox1 over-expression activated smooth muscle α−actin (SMαA) and smooth muscle myosin heavy chain (SM- MHC) promoter expression by 20- and 80-fold respectively, and Meox1 knockout ESCs showed markedly reduced activation of SMC differentiation marker genes including SMαA, SM-MHC, and SM22α in an ESC-EB model of SMC differentiation. Meox1 -/- mouse embryos exhibited decreased SMαA expression in neural crest-derived branchial arch arteries, but not in mesodermal tissues such as dorsal aorta. Taken together, results provide evidence that Meox1 plays an important role in regulating early stages of development of neural crestderived SMC.

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