Inactivation of upstream elements of the MAPK cascade results in analogous defects in neural crest development. Compared with WT controls (A–D), mandibular hypoplasia and maxillary truncation is observed in MEK1fl/fl MEK2−/− Wnt1:Cre E17.5 embryos (E and F). Disruption of MEK1/2 signaling also resulted in decreased crown–rump length, eye placement anomalies, absence of the tongue, and a disruption of external ear development (E and F). PTA was consistently detected in E16.5 cross-sections and dissected E17.5 MEK1fl/fl MEK2−/− Wnt1:Cre embryos (G and H). The conditional inactivation of B-Raf/C-Raf did not alter embryonic size or external ear development, but mandibular and maxilla hypoplasia (I and J) was observed. Analysis of B-Raffl/fl C-Raffl/fl Wnt1:Cre embryos revealed partial penetrance of cardiac defects. An E17.5 embryo is displayed (K) that clearly demonstrates PTA whereas cross-sections from the E16.5 embryo (L) show mild conotruncal defects, namely double-outlet right ventricle. Scale bars, 2 mm.