Cleft palate is one of the major malformations induced by excess RA in rodent models ([Cuervo et al., 2002] and references therein). Lack of fusion of the palatal shelves is also seen in compound Rara/Rarg mutants [Lohnes et al., 1994], and mice deficient for endogenous RA synthesis (P. Dollé, unpublished observations). All three Rars are expressed during palatal shelf development, with Rarb levels increasing by E13.5 [Naitoh et al., 1998]. Distinct Rar expression patterns have also been described during tooth bud development [Bloch-Zupan et al., 1994], although the functional involvement of RARs in odontogenesis remains unclear.
