RETINOIC ACID INDUCES STAGE-SPECIFIC ANTERO-POSTERIOR TRANSFORMATION OF ROSTRAL CENTRAL-NERVOUS-SYSTEM

We report a time-course analysis of the effect of retinoic acid (RA) o n the development of the mouse central nervous system (CNS) from the b eginning of gastrulation throughout induction and patterning of the ne ural tube. RA administration induces three different, stage-specific a lterations of brain development, indicating perturbation of different morphogenetic steps during the establishment of a neural pattern, In p articular, treatment at mid-late streak stage (7.2-7.4 days post coitu m (d.p.c,)) results in early repression of Otx2 expression in the post erior neuroectoderm of the head fold and in the ventral mid line, incl uding the prechordal plate and the rostralmost endoderm, followed by l oss of forebrain morphological and molecular identities, as revealed b y analysis of the expression of regionally-restricted brain genes (Otx 2, Otr1, Emx2, Emx1 and Dlx1). In these embryos, reduction of the Otx2 expression domain correlates with hindbrain expansion marked by rostr al extension of the Hoxb-1 expression domain, Our analysis indicates t hat RA interferes with the correct definition of both planar and verti cal morphogenetic signals at specific developmental stages by affectin g gene expression in the regions which are likely either to produce or to respond to these signals. We suggest that retinoids may contribute to early definition of head from trunk structures by selecting differ ent sets of regulatory genes,