In a recent study, Watanabe et al identify a novel enhancer in the fgf10 locus that is necessary and sufficient for expression in anterior second heart field. Their results suggest a competitive mechanism in which Isl1 and Nkx2-5 bind the enhancer to activate or repress this enhancer, respectively. In the last decade, new insights into heart development have demonstrated the existence of a second heart field, which gives rise to the second heart lineage.1,2 The first heart lineage is defined as the first cells to differentiate within the early cardiac crescent and forming heart tube, gives rise to a majority of cells within the left ventricle, and contributes to both atria. The second heart field progenitors actively proliferate and are progressively added to the heart to give rise to the right ventricle, outflow tracts, and to a majority of cells within the atria. As second heart field progenitors enter the heart, proliferation is downregulated concomitant with differentiation. Gene networks which regulate the transition from second heart field progenitor to differentiated myocyte have been the subject of intense scrutiny, particularly for anterior second heart field progenitors, which will contribute to the anterior pole of the heart.3–5 Pioneering work with an nLacZ transgene fortuitously integrated into the Fgf10 locus revealed the mammalian anterior second heart field.6 Expression of endogenous Fgf10 occurs first in the second heart field medial to the differentiating cells of the first lineage in the cardiac crescent. Its expression was later observed in the anterior second heart field comprising pharyngeal mesoderm dorsal and anterior to the heart, including core mesoderm of the first 2 pharyngeal arches.7,8 Fgf10 cooperates with Fgf8 to drive proliferation of the second heart field.3 To shed new light on gene networks regulating the transition …