Heads or tails? Retinoic acid will decide.

A recent study (Niederreither et al. Nat Genet 1999;21:444-448 [Ref. 1]) describes the phenotype of a gene knockout for an enzyme, retinaldehyde dehydrogenase 2 (RALDH-2), that synthesizes retinoic acid (RA) in the early embryo. The effects generated by this single enzyme mutation are remarkably similar to those previously described in vitamin A-deprivation studies and compound retinoic acid receptor knockouts, which involve multiple systems of the embryo. With other data on the distribution of RA, its role in axial specification of the early embryo is considerably clarified. Surprisingly, it seems that head development is unaffected in these RALDH-2 knockout embryos; thus, the anterior of the embryo does not require RA, despite the observations that the hindbrain seems exquisitely sensitive to RA perturbation. Head development may be realised by a cytochrome P450 enzyme (CYP26), which has been described recently. Between these two opposing forces, the hindbrain develops. Copyright 1999 John Wiley & Sons, Inc.