Islet-l is a LIM-homeodomain transcription factor that has been defined to label cardiac progenitor cells of the second heart field. Here we provide the first analysis of the expression pattern of Xenopus islet-l (Xisl-l) in the context of cardiovascular development. During early stages of heart development Xis1-1 is co-expressed with Nkx2.5 in the cardiac crescent in Xenopus supporting the notion of an initially single heart field. At subsequent stages of cardiogenesis the expression domains of Xisl-l and Nkx2.5 become more distinct with Xisl-l being detected more anterior to Nkx2.5, however both factors continue to be co-expressed in the dorsal mesocardium and pericardial roof of the linear heart tube. The presence of a cardiac Xisl-l progenitor pool in an amphibian whose heart lacks an anatomically separated right ventricle is intriguing. Functional analyses show that Xisl-l is required for normal heart development. Inhibition of Xisl-l results in defects in heart morphogenesis and in the downregulation of early cardiac markers implicating a role for Xisl-l in cardiac specification. Additionally, Xisl-l loss-of-function affects the expression of several vascular markers demonstrating the involvement of Xisl-l in vasculogenesis. (c) 2007 Elsevier Inc. All rights reserved.