As described above, none of the Rar murine gene transcripts were detected in the early embryonic neuroectoderm rostrally to the hindbrain, i.e., at midbrain and forebrain levels (e.g., Figure 2D,E and Figure 3B). This is surprising, since the RA-producing enzyme Raldh2 is transiently expressed in the rostralmost forebrain epithelium before outgrowth of the telencephalic vesicles, and Raldh2-/- knockout embryos have severe forebrain deficiencies [Ribes et al., 2006]. RALDH2 function is partly redundant with that of RALDH3, which produces RA in the frontonasal, non-neural surface ectoderm [Halilagic et al., 2007; Schneider et al., 2001]. Possibly, RAR(s) are expressed at low levels in the early forebrain neuroepithelium, where they might transduce these RA effects. Xenopus Rara is expressed during early brain development [Shiotsugu et al., 2004], and RAR knock-down in this species reduces forebrain development [Koide et al., 2001]. Also, one of the zebrafish Rara orthologues (rarab) is expressed in the prospective diencephalon [Hale et al., 2006].
