Abstract 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 mammals. The genes for some compo- nents of this cascade are located in chromosomal regions that are deleted in human syndromes associated with neural crest cell defects, like DiGeorge and Velo-Cardio- Facial Syndrome. These syndromes are often accompa- nied by abnormalities in cardiac morphology. Further- more, we have reported in previous studies the upregula- tion of the tissue polarity gene frizzled 2 in myofibro- blasts during their migration into the necrotic area after myocardial infarction in the adult heart. It is known that genes that are upregulated during cardiac remodeling due to pathology often play a role during development. To investigate whether frizzled 2 can be associated with the process of cardiac morphogenesis we studied its ex- pression in the thoracic arterial system and heart of mouse embryo’s of 10, 12, 14, 16 and 18 days after con- ception 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 trunk 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 expression was observed at any time point. Minor myocardial expression was observed in the ventricular septum at days 12 and 14. Atrial ex- pression, although considerably lower than ventricular expression, could be detected somewhat later at days 14 and 16. Our results indicate that there is transient expres- sion of frizzled 2 in areas that are invested by neural crest cells. This expression is downregulated upon neural crest cell differentiation. The frizzled 2 expression sup- ports a role for the Wnt-frizzled pathway in neural crest- related disorders. Keywords Neural crest · Frizzled · Cardiac morphogenesis · Apoptosis · Whole body in situ hybridisation · Wnt Introduction The mammalian homologues of Drosophila tissue-polar- ity gene ‘frizzled’ consist of a family with multiple members, all encoding seven transmembrane receptor proteins (Vinson et al. 1989). In developing Drosophila wings, transcripts of the ‘frizzled’ gene have been dem- onstrated to transduce and translate polarity signals for hair and bristle development on the epidermal cells, probably through an interaction with the cytoskeleton (Wong and Adler 1993). This involvement in the spatial control of wing hair polarity during development may suggest a similar role in architectural control in mam- mals. The current theory about the function of the friz- zled proteins is that they act as receptors for the Wnt proteins (Yang-Snyder et al. 1996). The function of the Wnt family has already been studied during mammalian embryology. It was observed that Wnt-1 and Wnt-3a sig- naling can regulate the dorsal-ventral patterning in mam- malian CNS through the control of cell proliferation (Ikeya et al. 1997). Furthermore, in in vitro assays that aimed at investigating neural crest induction by surface ectoderm, a correlation between appearance of Wnt-1 expression and migration of neural crest cells was found (Dickinson et al. 1995). The expression of the Wnt1 in early migrating neural crest cells and the observation that this gene is not expressed afterwards in any other place during development (Echelard et al. 1994) has been used to construct a Cre/lox neural crest reporter M.E. van Gijn · W.M. Blankesteijn · J.F.M. Smits Department of Pharmacology, Universiteit Maastricht, Maastricht, The Netherlands B. Hierck · A.C. Gittenberger-de Groot ( ✉ ) Department of Anatomy and Embryology Leiden University Medical Center, P.O. Box 9602, 2300 RC Leiden, The Netherlands, e-mail: acgitten@lumc.nl Tel./Fax: +31-71-5276661/5276680 Anat Embryol (2001) 203:185–192 © Springer-Verlag 2001 ORIGINAL ARTICLE Marielle. E. van Gijn · W. Matthijs Blankesteijn Jos F.M. Smits · Beerend Hierck Adriana C. Gittenberger-de Groot Frizzled 2 is transiently expressed in neural crest-containing areas during development of the heart and great arteries in the mouse Accepted: 27 October 2000