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Figure 4


Fig. 4. OFT remodeling is sensitive to Fgfr1/2 gene dosage in mesodermal OFT precursors and pharyngeal endoderm. Whole-mount thorax dissections (A-H) and sectioned preparations (A'-H') of mouse embryos at E18.5. R1, Fgfr1; R2, Fgfr2. (A,A') Double homozygous conditional control with normal relationships of atria (LA, left atrium; RA, right atrium), ventricles (LV, left ventricle; RV, right ventricle), aorta (Ao), main pulmonary artery (PA), pulmonary valve (PV), right and left subclavian arteries (RSA, LSA) and right and left common carotid arteries (RCC, LCC). The normal shape of the RV conus (co) is indicated by the dashed line in E. These anatomic annotations are used in this and all subsequent figures. (B,B') Normal Fgfr1c/+;Fgfr2c/c;Mesp1Cre OFT. (C,C') Fgfr1c/c;Fgfr2c/+;Mesp1Cre embryo with the DORV alignment defect (double arrowhead). Hypoplasia of the RV conus (dashed line) causes the aortic valve (AV) and PV to be abnormally located in the same plane (C'). The aortic arch is interrupted (arrowhead). (D,D') Fgfr1c/c;Fgfr2c/c;Mesp1Cre embryo with type III PTA: the aortic arch and left and right branch pulmonary arteries (LPA, RPA) arise from the unseptated truncus arteriosus (TA). The truncal valve (TV) is committed to the RV (arrowhead). ca, coronary artery. (E,E') Normal OFT in an Fgfr1c/+;Fgfr2c/+;Isl1Cre double heterozygote. (F,F') Fgfr1c/+;Fgfr2c/c;Isl1Cre mutant with conal hypoplasia (dashed line) and misaligned Ao and PA. (G,G') Fgfr1c/c;Fgfr2c/+;Isl1Cre, type I PTA with pentacuspid TV (G') and interrupted aortic arch (arrowhead). (H,H') Fgfr1c/c;Fgfr2c/c;Isl1Cre mutants have type III PTA. This TV is bicuspid and arises from the RV (H').