limb bud cells by the RALDH2 enzyme, from which it likely acts in conjunction with posteriorly-restricted factors (such as Hand2) to induce a functional ZPA [Mic et al., 2004; Niederreither et al., 2002]. Another, later function of RA concerns the involution of the interdigital mesenchyme (Figure 5). Rarb (mainly the Rarb2 isoform) is specifically expressed in the prospective interdigital zones of the fore- and hindlimbs (Figure 5B,C), similar to the RA-synthesizing enzyme RALDH2 [Dolle et al., 1989; Mollard et al., 2000; Niederreither et al., 1997]. Abnormal interdigital webbing is indeed seen in several Rar and/or Rxra compound mutant genotypes ([Dupe et al., 1999a] and references therein).
