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Isl1 Expression at the Venous Pole Identifies a Novel Role for the Second Heart Field in Cardiac Development

From the Department of Cell Biology and Anatomy (B.S.S., J.L.O., M.R.C., E.E.W., A.L.P., S.W.K., A.W.) Medical University of South Carolina, Charleston; and the Department of Pediatrics (S.W.K., A.W.), Division of Pediatric Cardiology, Medical University of South Carolina, Charleston.

Correspondence to Andy Wessels, PhD, Department of Cell Biology and Anatomy, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425. E-mail wesselsa{at}musc.edu

The right ventricle and outflow tract of the developing heart are derived from mesodermal progenitor cells from the second heart field (SHF). SHF cells have been characterized by expression of the transcription factor Islet-1 (Isl1). Although Isl1 expression has also been reported in the venous pole, the specific contribution of the SHF to this part of the heart is unknown. Here we show that Isl1 is strongly expressed in the dorsal mesenchymal protrusion (DMP), a non–endocardially-derived mesenchymal structure involved in atrioventricular septation. We further demonstrate that abnormal development of the SHF-derived DMP is associated with the pathogenesis of atrioventricular septal defects. These results identify a novel role for the SHF.

Key Words: Isl1 • Nkx2.5 • dorsal mesenchymal protrusion • second heart field • venous pole • vestibular spine

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