Disruption of TGF-β superfamily signaling by either complete or conditional inactivation of Bmp4, TGF-β2, TGF-βR2, Alk5, Alk2 or Smad4 results in abnormal development of Meckel's cartilage and mandible, which lead to cleft palate.19, 32, 33, 34, 35, 36, 37 In the present study, we found that Tfrc deletion in NCCs dramatically suppresses both TGF-β and BMP signaling. This evidence concerns the gene SMAD4 and cleft palate.