In this study, we have deleted the TGF-β type I receptor (Alk5) gene specifically in the mouse neural crest (NC) cell lineage. Our data suggest that ALK5 is required cell autonomously in the NC to mediate non-redundant signaling events that are essential for appropriate patterning of the pharyngeal organs and cardiac OFT. The cardiac and pharyngeal defects observed in the NC-specific Alk5 mutants differ significantly from those seen in corresponding mutants lacking the TGF-β type II receptor, suggesting that signaling mediated by ALK5 is not limited to the classical TGF-β ligands during cardiac/pharyngeal development.