a Schematic of Hand gene expression during early cardiac development. Published findings describe early expression within the anterior later plate mesoderm, which in the chick persists for both Hand genes. In mouse, Hand2 persists until E8.0 and upon rightward looping, restricts to second field lineage cells on the right ventricle and OFT. Hand1 prior to heart tube fusion already displays chamber-specific expression within the primary heart field derived left ventricle and OFT such that by E9.5 coexpression with the myocardial cuff and OFT is observed along with unique expression domains that define the left and right ventricles. b Schematic of Hand1 and Hand2 coding regions showing amino acid identities within the amino terminal, bHLH, and carboxy terminal domains. The positions of the basic DNA-binding domain are shown in black and poly-histidine and polyalanine tracks in the amino terminal portion of each respective protein are indicated. The evolutionarily conserved threonine and serine within Helix I of the bHLH are phosphoregulated via PKA and B56d-containing PP2A. Regulation alters dimer partner choice and effects DNA-binding affinities to various cis-elements. Amino acid alignment of Hand1 and 2 over the basic domain and Helix I showing high level of conservation within the DNA binding and dimerization motifs