During the last few years the Wnt1-Cre transgenic driver line has proven to be a powerful tool for tissue-specific gene deletion in NCCs [12,13,27,28]. Using this approach, several studies have independently shown that the NC-specific deletion of the Tgfbr2 gene leads to a distinct set of calvarial, facial and cardiac defects [8,9,20,29]. Interestingly, these defects appear quite different both in the craniofacial and pharyngeal regions, including the heart, when compared to the corresponding mutants of Alk5, which encodes the TGF-β type I receptor, a prototypical binding partner of TGF-βRII [19] and the present study). While Tgfbr2/Wnt1-Cre mutants as well as mice deficient in Tgf-β2 display the PTA type A4 (truncus arteriosus with interrupted aortic arch [30]), Alk5/Wnt1-Cre mutants reported here demonstrate earlier patterning defects of the PAAs, which is particularly obvious in the 3rd pair of the PAAs. Moreover, the Alk5/Wnt1-Cre mutants display an abnormal patterning of the aortic sac and defective AP septation leading to PTA, reminiscent of type A2 (= truncus artriosus with no main pulmonary artery segment present [30]). However, our results also demonstrate that significant hypoplasia of the aortic sac leads to a severe shortening of the ascending truncal arch, which masks possible defects in derivatives of the 4th PAAs, i.e., interruption of the aortic arch. These observed differences are likely due to substantial apoptosis of Alk5-deficient post-migratory neural crest cells, which is clearly detectable at E10.5, whereas similar intense cell death has not been reported in Tgfbr2/Wnt1-Cre mutants[9].