Autonomous and non-cell autonomous role of cilia in structural birth defects in mice
Fig 7
Late tamoxifen deletion of Ift140 with CAGGCre-ER uncovers additional phenotypes.
Ift140flox/+, CAGGCre-ER+ (Control) (A, D, G, J, L) and Ift140flox/null1, CAGGCre-ER+ experimental (B, C, E, F, G, H, K, M, N) embryos were treated with tamoxifen at E7.5 or E8.5 and harvested at E16.5. E7.5 tamoxifen-dosed embryos show severe gastroschisis with the majority of the abdominal organs protruding from the abdominal cavity (A, B, D, E). E8.5 dosed embryos show only moderate gastroschisis with only some of the abdominal organs found outside of the abdominal cavity (A, C, D, F). Both E7.5 and E8.5 dosed embryos showed significant hydrops (* B, C, E, F), polydactyl (H, I), and hypoplastic lungs (B, C, E, F). Laterality defects were not observed in either E7.5 or E8.5 tamoxifen-dosed embryos, with all hearts displaying a normal D-looping phenotype (J, K). However, cardiac defects were observed in the experimental animals including ventricular septal defects (J, K) and AVSDs (L, M). (N) While the great vessels of both E7.5 and E8.5 tamoxifen-dosed experimental embryos displayed normally septated aorta and pulmonary trunk, approximately 50% had great artery patterning defects including: right aortic arch, interrupted aorta (arrows), hypoplastic transverse aorta (arrowhead), hypoplastic pulmonary arteries (*), and in 1 case double aortic arch with both left and right descending aortas. A: aorta; P: pulmonary trunk; LV: left ventricle; RV: right ventricle; LA: left atria; RA: right atria; t: trachea; o: esophagus; VSD: Ventricular septal defect; AVSD: atrioventricular septal defect; cx: cerebral cortex; sc: spinal cord; mb: midbrain; fl: forelimb; hl: hindlimb; e: eye; forebrain; op: otic placode; hf: hair follicles; RCA: right carotid artery; LCA: left carotid artery; LSA: left subclavian artery; LdAo: left descending aorta; RdAo: right descending aorta; RPA: right pulmonary artery; LPA: left pulmonary artery; Ao: aorta; P: pulmonary trunk; lv: liver; ln: lungs; s: stomach; i: small intestine. Scales bars: A–I = 1 mm, J–M = 0. 5 mm.