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(greater than or equal to 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.