Fig. 6. Ablation of FGF8 in the PA endoderm and ectoderm by hoxa3-IRESCre reveals that endodermal domain-specific FGF8 activity is required for thymic, parathyroid and aortic valve formation. (A) Sections through neck of E18.5 control. Note the large parathyroid gland (pth) embedded in posterior-lateral aspect of thyroid (tyr). e, esophagus; tr, trachea. (B-D) Parathyroid ectopy and/or hypoplasia in Fgf8/hoxa3-IRESCre mutants. c, clavicle. (E) Wild-type control with normal bi-lobed thymus. (F,G) Thymic hypoplasia and migration defects in Fgf8/Hoxa3-IRESCre mutants. (F) Hypoplastic left thymus in association with a right aortic arch (raa). (G) Monolobed ectopic gland. (H) Cross-section of normal aortic valve in control animal, anterior is towards the left; note three cusps: right (R), left (L), posterior (P). (I-K) Bicuspid aortic valves in Fgf8/Hoxa3-IRESCre mutants. (L) Cross-section through the right ventricular outflow tract of a control embryo showing the relationship of the aorta (Ao), pulmonary valve (PV) and right ventricle (RV). (M-O) Sections through an animal with Tetralogy of Fallot (TOF). (M) Dysplastic PV and severe subvalvar and infundibular stenosis. (N) Cross-section of the left ventricular outflow tract (LVOT), right ventricle (RV) and intact ventricular septum in a wild type animal; there is continuity between the aortic (Ao) and mitral (mv) valves. Note thickness of right ventricular free wall and ventricular septum (yellow bidirectional arrows); the heart is fixed in late systole (mitral valve is closed). (O) The mutant displays overriding aorta (both the right and left ventricular outflow tracts empty through the aortic valve), right ventricular hyperplasia with marked increase in thickness of the right ventricular wall and ventricular septum (yellow bidirectional arrows, heart in late systole), and a large membranous ventricular septal defect (red arrowhead).