Mice deficient in growth differentiation factor 11 (GDF11) signaling display anterior transformation of axial vertebrae and truncation of caudal vertebrae. However, the in vivo molecular mechanisms by which GDF11 signaling regulates the development of the vertebral column have yet to be determined. We found that Gdf11 and Acvr2b mutants are sensitive to exogenous RA treatment on vertebral specification and caudal vertebral development. We show that diminished expression of Cyp26a1, a retinoic acid inactivating enzyme, and concomitant elevation of retinoic acid activity in the caudal region of Gdf11−/− embryos may account for this phenomenon. Reduced expression or function of Cyp26a1 enhanced anterior transformation of axial vertebrae in wild-type and Acvr2b mutants. Furthermore, a pan retinoic acid receptor antagonist (AGN193109) could lessen the anterior transformation phenotype and rescue the tail truncation phenotype of Gdf11−/− mice. Taken together, these results suggest that GDF11 signaling regulates development of caudal vertebrae and is involved in specification of axial vertebrae in part by maintaining Cyp26a1 expression, which represses retinoic acid activity in the caudal region of embryos during the somitogenesis stage.

Introduction: Systemic venous circulation anomalies are uncommon; they are often incidental findings during echocardiography. Case: A 56-year-old man, with dextrocardia, was evaluated for dyspnea. The patient's medical history included diabetes mellitus requiring insulin treatment, hypertension, and tobacco use. Physical examination revealed normal jugular venous pulsations and clear lungs. Cardiac examination revealed normal heart sounds, and grade II/VI systolic ejection murmur over the right precordium. Echocardiography revealed normal chamber size and systolic function, without significant valvular lesions. The coronary sinus was dilated. It was evaluated using intravenous agitated saline contrast to rule out anomalous venous drainage or shunting. When injected into the left antecubital vein, contrast appeared initially in the right atrium followed by the right ventricle. However, when injected into the right antecubital vein, contrast appeared initially in the dilated coronary sinus followed by the right atrium and right ventricle. There was no evidence of intracardiac shunting. These findings were consistent with persistent right superior vena cava in the setting of situs inversus dextrocardia, with normally draining left superior vena cava. Conclusion: Persistent superior vena cava connection to the coronary sinus is often incidental but an important finding which helps in planning safe invasive procedures.