Islet 1 is expressed in distinct cardiovascular lineages, including pacemaker and coronary vascular cells

Abstract

Islet1 (Isl1) is a LIM homedomain protein that plays a pivotal role in cardiac progenitors of the second heart field. Here, lineage studies with an inducible isl1-cre demonstrated that most Isl1 progenitors have migrated into the heart by E9. Although Isl1 expression is downregulated in most cardiac progenitors as they differentiate, analysis of an isl1-nlacZ mouse and coimmunostaining for Isl1 and lineage markers demonstrated that Isl1 is expressed in distinct subdomains of the heart, and in diverse cardiovascular lineages. Isl1 expression was observed in myocardial lineages of the distal outflow tract, atrial septum, and in sinoatrial and atrioventricular node. The myocardialized septum of the outflow tract was found to derive from Isl1 expressing cells. Isl1 expressing cells also contribute to endothelial and vascular smooth muscle lineages including smooth muscle of the coronary vessels. Our data indicate that Isl1 is a specific marker for a subset of pacemaker cells at developmental stages examined, and suggest genetic heterogeneity within the central conduction system and coronary smooth muscle. Our studies suggest a role for Isl1 in these distinct domains of expression within the heart.

Expression of Id2 in the second heart field and cardiac defects in Id2 knock‐out mice

“…Remarkably, expression of several other genes involved in heart development is observed in myocardial and neural crest lineages, and in the endoderm, including Isl1 (Sun et al, 2007;Cai et al, 2003) and Tbx3 (Mesbah et al, 2008a). Additionally, Id2 was observed in components of the ventricular cardiac conduction system, as described previously (Moskowitz et al, 2007).…”

Defining the earliest step of cardiovascular progenitor specification during embryonic stem cell differentiation

“…Interestingly, in Ciona intestinalis, a prim itive chordate, a fraction of Mesp1 expressing cells coexpresses Isl1 (Stolfi et al, 2010), suggesting that the expression of Isl1 in a subpopulation of the Mesp1 field has been conserved through out vertebrate evolution. In vertebrates, several recent studies showed that Isl1 is expressed transiently in the progenitor of the FHF during embryonic development, and some Isl1 derived cells can give rise to both FHF and SHF derivatives (Brade et al, 2007;Prall et al, 2007;Sun et al, 2007;Ma et al, 2008). …”

Stem cells in the heart: What's the buzz all about?—Part 1: Preclinical considerations

“…22 Laugwitz et al 23 demonstrated the presence of an Isl-1 + population of cardiac stem cells in the postnatal mouse, rat, and human heart, most prominently in the outflow tract and right atrium. Further studies showed that Isl-1 marks a population of multipotent cardiac stem cells contributing to smooth muscle, endothelial, and pacemaker cell lineages in the embryonic and postnatal heart 24,25 and implicate Isl-1 + Nkx2.5 + Flk-1 + cells as the most primitive cardiac stem cells. No compelling evidence for an Isl-1 + population in the adult heart has been presented.…”