Fig. 8. The roles of Hand genes in ventricular development. Knockout mice lacking Hand2 have demonstrated the essential role of this gene in formation of the RV. Knockout mice lacking Nkx2.5 show a loss of the LV and downregulation of Hand1. Knockout mice lacking Hand1 show relatively minor abnormalities in the LV, suggesting that the loss of Hand1 alone is insufficient to account for the more severe LV defects in Nkx2.5 mutant embryos. Knockout mice lacking both Hand1 and Hand2 show severe ventricular hypoplasia, suggesting redundant functions of the Hand genes in the developing LV.