Retinoic acid affects central nervous system development of Xenopus by changing cell fate

Retinoic acid (RA) may play a role in anterior-posterior (A-P) patterning in the central nervous system (CNS) of vertebrates. To understand this role, Xenopus embryos were treated with increasing doses of all-trans RA at the late gastrula to early neurula stage, and changes in the brain were assessed. When embryos were treated with a low dose of 10(-8) M RA, alterations of the brain were observed: a 120% increase in the expression of a neural-specific marker, XlPOU 1, in the brain and eye with a concurrent loss of the forebrain. Higher doses of RA led to progressively more severe truncations in the brain and a loss of XLPOU 1 expression. Most importantly, after observing changes in the RA-treated embryos, we determined that the lineage of cells that contribute to the brain of these embryos do not die but change their fate. With higher doses of RA (> or = 10(-7) M), the normal cell fate of the A1 lineage was changed from a mostly neuronal phenotype to an epidermal one. Our data suggest that exogenous RA or a closely related derivative causes changes in cell fate of the A1 lineage which may in part be responsible for alterations in the developing CNS.