JCI - Murine Jagged1/Notch signaling in the second heart field orchestrates Fgf8 expression and tissue-tissue interactions during outflow tract development

Murine Jagged1/Notch signaling in the second heart field orchestrates Fgf8 expression and tissue-tissue interactions during outflow tract development

Frances A. High, Rajan Jain, Jason Z. Stoller, Nicole B. Antonucci, Min Min Lu, Kathleen M. Loomes, Klaus H. Kaestner, Warren S. Pear, Jonathan A. Epstein

Published in Volume 119, Issue 7

J Clin Invest. 2009; 119(7):1986–1996 doi:10.1172/JCI38922

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Figure 1

Cardiovascular defects in Notch second heart field mutants.

E17.5–P0 control (A), Islet1^Cre/+;DNMAML (B and C), and Mef2c-AHF-Cre;DNMAML (D–F) mutants. (A) Arrows indicate pulmonary artery and aorta. (B) A single OFT vessel (arrow) and retroesophageal right subclavian artery. (C) Double outlet right ventricle (arrows) with a right aortic arch and left ductus arteriosus producing a vascular ring. (D) Cervical right aortic arch (arrow). (E) Interruption of the aortic arch, type B (IAA-B, arrow), and retroesophageal right subclavian artery. (F) Double aortic arch (arrows). (G–P) H&E sections of E17.5–E18.5 hearts. (G) Control with separate aorta and pulmonary artery. (H) Islet1^Cre/+;DNMAML mutant with single OFT arising from right ventricle. (I) Islet1^Cre/+;DNMAML mutant with retroesophageal right subclavian artery dorsal to the trachea. (J and K) Sections from a Mef2c-AHF-Cre+;DNMAML mutant showing a vascular ring. A right-sided circumflex arch (J) runs posterior to the trachea and esophagus en route to a left-sided descending aorta and left ductus arteriosus (K). (L) Control with normal tricuspid valve (arrow). (M and N) Islet1^Cre/+;DNMAML with tricuspid atresia (arrow, M), right ventricular hypoplasia, and atrial septal defect (arrow in N). (O and P) Islet1^Cre/+;DNMAML (O) and Mef2c-AHF-Cre+;DNMAML (P) hearts showed ventricular septal defects (arrows). ao, aorta; da, ductus arteriosus; e, esophagus; IAA-B, interruption of the aortic arch, type B; la, left atrium; lca, left carotid artery; lsa, left subclavian artery; lv, left ventricle; pa, pulmonary artery; pv, pulmonic valve; ra, right atrium; rca, right carotid artery; rersa, retroesophageal right subclavian artery; rsa, right subclavian artery; rv, right ventricle; ta, truncus arteriosus; tr, trachea; tv, tricuspid valve. Original magnification: ×30 (A–F). Scale bars: 250 μm (G–K), 500 μm (L–P).