Defects in large arteries and the cardiac outflow tract in GPR116-ELTD1 double deficient embryos (E18.5).

(A) H&E staining of thoracic sections from two individual Gpr116^-/-;Eltd1^-/- embryonic mice with enlarged views of the areas marked by dashed lines shown below. Asterisks indicate the position of the ventricle septum defect. LV, left ventricle; RV, right ventricle. (B) Ventral view of large vessels in a Gpr116^-/-;Eltd1^-/- embryonic mouse and a control littermate (Gpr116^-/-;Eltd1^+/+) with large arteries marked by dashed lines. A schematic of arteries is shown below. Arrow points to the position where the right subclavian artery usually branches off. 1, Aortic arch; 2, Innominate artery; 3, Right subclavian artery; 4, Left common carotid artery; 5, Ascending thoracic aorta; 6, pulmonary artery. (C) Schematic of the embryonic remodeling process of the branchial arch arteries into the aortic arch and the great vessels in normal configuration (E10.5 and E18.5) as well as in disease examples showing aberrant right subclavian artery, interrupted aortic arch and double aortic arch. RSA and LSA, right and left subclavian artery; RCA and LCA, right and left common carotid artery; A, aorta; da, ductus arteriosus; PT, pulmonary trunk. (D) Representative ventral view of large vessels from a Gpr116^-/-;Eltd1^-/- embryonic mouse and a control littermate (Gpr116^+/-;Eltd1^-/-) with arteries indicated by dashed lines. A schematic of arteries is shown below. 1. Ascending aorta; 2. Aortic arch; 3. Pulmonary artery; 4. Right subclavian artery; 5. Right common carotid artery; 6. Left common carotid artery; 7. Left subclavian artery. 2, 3 and 7 are highlighted in yellow indicating interrupted aortic arch. (E) H&E staining of thoracic cross sections (from inferior (left) to superior (right)) from a Gpr116^-/-;Eltd1^-/- embryonic mouse with enlarged views of the dashed line areas shown below. The aorta is connected to the right ventricle, which leads to double outlet right ventricle (DORV). LV, left ventricle; RV, right ventricle. (F) H&E staining of thoracic cross sections (from inferior (left) to superior (right)) from a Gpr116^-/-;Eltd1^-/- embryonic mouse with enlarged views of the areas indicated by a dash line shown below, exhibiting a double aortic arch with a retro-esophageal segment. Os, oesophagus; T, trachea; A, aorta. Scale bars: 200 μm (A, E, F).