XENOPUS HINDBRAIN PATTERNING REQUIRES RETINOID SIGNALING

We have asked how posterior neural tissue is patterned in Xenopus by a ssaying the involvement of endogenous retinoic acid (RA) in this proce ss and by using the labial Hox gene, HoxD1, as a posterior marker. Alt hough RA is able to inhibit anterior gene expression and activate expr ession of more posterior genes, the normal role of retinoids in antero posterior (A/P) patterning is unclear. HoxD1 is an early posterior neu rectodermal marker, expressed from midgastrula with a later anterior e xpression limit in the future hindbrain. We previously showed that Hox D1 was induced as an immediate early response to retinoic acid in naiv e ectoderm (animal caps). Here, we use a truncated RAR alpha 2.2 recep tor (RAR Delta) to dominantly interfere with retinoid signaling. In em bryos injected with RAR Delta expression of HoxD1 is eliminated. Conju gates of ectoderm and dorsolateral mesoderm show that retinoid recepto rs are required in the ectoderm for HoxD1 induction. Further, expressi on of Krox-20 in r3 and r5 of the presumptive hindbrain is compressed into a single stripe that suggests elimination of r5. RAR alpha 2.2 ex pression almost precisely overlaps that of HoxD1, suggesting that this receptor may normally activate HoxD1. Expression of neither more ante rior genes including cement gland, forebrain, and midbrain markers nor a more posterior spinal cord marker is affected by RAR Delta. These d ata suggest that the posterior hindbrain is the region of the nervous system most sensitive to retinoid loss. Finally, we compare the abilit y of RA and fibroblast growth factor (FGF) to posteriorize isolated an terior neurectoderm and show that both factors can act directly on thi s substrate. RA acts in a more anterior domain than does FGF; however, neither factor is equivalent to the natural posteriorizing capacity o f the posterior mesoderm. We propose that endogenous retinoid and FGF signals pattern largely nonoverlapping regions along the A/P axis and that posterior neural patterning requires multiple inducers. (C) 1997 Academic Press.