The transcription factor MEF2C-null mouse exhibits complex vascular malformations and reduced cardiac expression of angiopoietin 1 and VEGF

The MEF2 family of transcription factors has been implicated in transcripti onal regulation in a number of different cell types. Targeted deletion of t he MEF2C gene, in particular, revealed its importance for early cardiogenes is (Q. Lin ct al., 1997, Science 276, 1404-1407). We report here that this deletion also resulted in vascular anomalies characterized by extreme varia bility in lumen size and defects in remodeling. While primary vascular netw orks formed in the yolk sac of the mutants, they failed to remodel into mor e complex vascular structures. Likewise, although the primordia of the dors al aortae formed normally, anomalies were observed in these vessels later i n development. Dorsal and anterior to the heart, the aortae exhibited abnor mally small lumens, as did the anterior cardinal veins and intersegmental a rteries. In contrast, the dorsal aortae and intersegmental arteries caudal to the heart were grossly enlarged. Cranial vessels were also enlarged and less branched than normal. Endocardiogenesis in the mutant was abnormal wit h the endothelial cells exhibiting a number of aberrant phenotypes. These e ndocardial defects were accompanied by a notable reduction in angiopoietin 1 and VEGF mRNA production by the myocardium, indicating that MEF2C is requ ired for myocardial expression of these important endothelial-directed cyto kines and thus for correct endocardial morphogenesis. (C) 1999 Academic Pre ss.