The heart is a major target organ of retinoid signaling during development, with RA being involved in morphogenetic events [Dickman and Smith, 1996; Niederreither et al., 2001; Zile et al., 2000], outflow tract septation and large vessel patterning [Ghyselinck et al., 1998; Gruber et al., 1996; Mendelsohn et al., 1994b] and regulation of cardiomyocyte differentiation [Kastner et al., 1997; Niederreither et al., 2001]. Gene knockout studies have highlighted the receptors involved in these processes (for review and references, see [Mark et al., 2009]), in particular they have revealed an important function of RARβ isoforms for the development of conotruncal ridges [Ghyselinck et al., 1998]. RXRα, on the other hand, is indispensable for proper cardiomyocyte differentiation and development of the trabecular myocardium. The exact tissue- and cell-types where retinoid-induced effects take place are not fully characterized, although a recent conditional gene knockout study has demonstrated that RXRα function is critical within the epicardium [Merki et al., 2005]. RA has also been shown to be required for proper morphogenesis and remodeling of the extra-embryonic vascular network, and RARα isoforms are thought to be involved in this process [Bohnsack et al., 2004].
