Although ∼1% of humans are born with structural heart malformations, we know relatively little about the transcriptional programs that underpin the complex, orchestrated process of heart development. Now three papers in Development report that the T-box transcription factor Tbx20 occupies a central position in the pathways that control heart lineage specification and morphogenesis, from where it acts dose-dependently to influence embryonic heart development and adult heart function. Richard Harvey's (see p. 2451) and Sylvia Evans' (see p. 2475) groups both used gene targeting in mice to investigate Tbx20's role in cardiogenesis. Both report that Tbx20 null mice die in mid-gestation with severely malformed, underdeveloped hearts in which heart chamber formation had failed. Underlying these defects is a perturbed transcriptional program that alters cell proliferation patterns, the expansion of cardiac progenitors and the acquisition of tissue identity. In particular, both teams found that Tbx2 – a transcriptional repressor that inhibits chamber-specific gene expression programs in non-chamber heart tissue – is inappropriately activated throughout the heart in Tbx20 null mice. These and other data lead Harvey and co-workers to propose that hierarchical, repressive interactions between Tbx20 and other T-box factors underlie the early lineage split between chamber and non-chamber myocardium on which subsequent heart morphogenesis depends. These conclusions are strengthened by the findings of Evans' team, who show that Tbx2 is a direct target of Tbx20. Moreover, they report that Tbx2 directly binds to Nmyc1, which it represses in vitro and which is required for early myocardial proliferation. Nmyc1 expression is also downregulated in Tbx20^-/- mice. From their findings, these authors conclude that Tbx20 regulates cell proliferation in a region-specific manner by repressing Tbx2, which in turn represses Nmyc1. Thus, these two studies reveal how Tbx20 co-ordinates the transcriptional programs that control heart tissue specification and growth. Harvey and co-workers' further finding that heart function is compromised in adult Tbx20^+/– mice adds additional complexity to this picture. The dose-dependent effects of Tbx20 are elegantly expanded upon by Benoit Bruneau and co-workers (see p. 2463). This group knocked down Tbx20 in ES cells using RNAi, and then generated mouse embryos from cell lines in which Tbx20 was expressed highly, moderately or not at all. Their findings show that Tbx20 acts in a dose-dependent manner during heart and motoneuron development – the complete knockdown of Tbx20, for example, mirrors the null mutant, while a mild knockdown causes right ventricle underdevelopment and persistent truncus arteriosus, defects associated with human heart congenital conditions. The breakdown of cardiac transcription factor networks also features in this study. Specifically, this team found that Tbx20 might act synergistically with the cardiac transcription factors Isl1 and Gata4 to activate Mef2c and Nkx2. 5 expression – genes that are required for anterior heart field formation, a region that gives rise to the heart's outflow tract and ventricles. Together, these papers shed new light on how tissue specification, morphogenesis and proliferation are co-ordinated in early heart development by Tbx20, and provide new candidates for the study of both congenital heart defects and adult cardiomyopathies.