Holt-Oram syndrome and Duane-radial ray syndrome, which we discuss in Box 3, present similar phenotypes due to genetic perturbations in a shared molecular pathway (Harvey and Logan, 2006): Tbx5 acts directly upstream of Sall4 during heart and appendage development in mice (Koshiba-Takeuchi et al., 2006) and in zebrafish (Harvey and Logan, 2006). The gene discussed is TBX5; the disease is Holt-Oram syndrome.