Frizzled 2 is transiently expressed in neural crest-containing areas during development of the heart and great arteries in the mouse

Frizzled 2 acts as a 7-transmembrane receptor in the Wnt-Dishevelled signal transduction cascade. Among others, this cascade has been associated with neural crest cell proliferation and early migration during development in m ammals. The genes for some components of this cascade are located in chromo somal regions that are deleted in human syndromes associated with neural cr est cell defects, like DiGeorge and Velo-Cardio-Facial Syndrome. These synd romes are often accompanied by abnormalities in cardiac morphology. Further more, we have reported in previous studies the upregulation of the tissue p olarity gene frizzled 2 in myofibroblasts during their migration into the n ecrotic area after myocardial infarction in the adult heart. It is known th at genes that are upregulated during cardiac remodeling due to pathology of ten play a role during development. To investigate whether frizzled 2 can b e associated with the process of cardiac morphogenesis we studied its expre ssion in the thoracic arterial system and heart of mouse embryo's of 10, 12 , 14, 16 and 18 days after conception by means of in situ hybridization. At day 10 after conception signal could be found in the pharyngeal arches and arch arteries. The outflow tract, the ascending aorta and the pulmonary tr unk were positive for frizzled 2 from day 12 on. This expression decreased with time and at day 18 only some signal could be detected in the aorta and pulmonary trunk. In contrast, in coronary and pulmonary arteries no expres sion was observed at any time point. Minor myocardial expression was observ ed in the ventricular septum at days 12 and 14. Atrial expression, although considerably lower than ventricular expression, could be detected somewhat later at days 14 and 16. Our results indicate that there is transient expr ession of frizzled 2 in areas that are invested by neural crest cells. This expression is downregulated upon neural crest cell differentiation. The fr izzled 2 expression supports a role for the Wnt-frizzled pathway in neural crest-related disorders.