NCC ablation in the chick has been shown to lead to PTA and to a failure of addition of myocardium from the secondary heart field [40]. It was suggested that the defective migration of cells from the secondary heart field to the OFT in turn resulted in shortening and inappropriate rotation of the OFT, leading to mal-alignment of the arterial pole with the ventricles [41]. While the detected OFT phenotype in Alk5/Wnt1-Cre mutants shared many similarities with that seen in the chick NC ablation models, e.g., PTA and the hypoplastic aortic sac, our current results suggest that the secondary heart field is not severely affected in Alk5 mutants (data not shown). Since we could not detect appropriate rotation of the OFT in neural crest-specific mutants of Alk5 or Alk2, it appears that cells derived from the NC, as well as those from the SHF, are mutually required for proper OFT rotation in mice. However, it appears that these two TGF-β/BMP type I receptors contribute to OFT rotation through different mechanisms. In Alk5 mutants there is very little, if any, detectable septal mesenchyme present, and thus it could be argued that in these mutants OFT rotation fails due to a lack of penetration of septal prongs into the cushion mesenchyme. In contrast, in Alk2/Wnt1-Cre mutants a sizeable septal mesenchyme could be seen, still without any obvious looping of the aortic sac and truncal OFT, suggesting that the mere presence of the septal mesenchyme, without correct smooth muscle cell differentiation, is not sufficient for OFT rotation.