Islet-1-Expressing Cells in Cardiac Development: Where Does It End?

W ork in the mouse has supported a fairly extensive role for islet-1-expressing cells in cardiac development of the outflow tract (OFT), atria, right ventricle (RV), and, to a lesser degree, the left ventricle (LV) [1]. However, in a recent article published in this journal by Genead and colleagues, this was challenged. Based on the distribution of islet-1-expressing cells during rat cardiogenesis (Isl1+ cells being present predominantly in the OFT and right atria (RA) but absent from the LV, the authors implied that the role of islet-1-positive cells in cardiac development is more limited than previously suggested by studies in the mouse [2]. This discrepancy they suggested might be due to techniques employed; the examination of mRNA expression rather than protein expression. In a study of early first trimester human embryonic heart (gestational weeks 5.5–9.0), Genead and colleagues again looked for the presence of islet-1-expressing cells (based on protein expression) and reported Isl1+ cells as being present mainly in the OFT but also in the atria and RV [3]. While Bu and colleagues described a similar pattern of islet-1 expression in the developing fetal human heart at 11 and 18 weeks of gestation, Isl1+ cells (again based on protein expression) being observed in the RA, OFT, left atrial (LA) wall, and appendage [4]. In a recent study we examined both the developing embryonic and fetal human heart for islet-1 at both the protein and mRNA levels. We noted the presence of transcript throughout development in the LV, RV, RA, LA, and OFT and protein expression in all these regions of the developing human heart, though at low levels in the LA and both the ventricles compared with the RA and OFT [5]. Perhaps the most obvious difference between our observations in the human and studies in the mouse versus that of these other human studies and the rat study is the presence of Isl1+ cells in the LV. What then are we to make of these differences? Can it simply be related to species variation, differences in stages of development or differences, and/or limitations in techniques used? It seems the extent of Isl1 progenitor contribution to cardiogenesis is as yet unresolved.