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First published online 5 May 2004
doi: 10.1242/dev.01129

Development 131, 2653-2667 (2004)
Published by The Company of Biologists 2004
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Multiple points of interaction between retinoic acid and FGF signaling during embryonic axis formation

Jason Shiotsugu1,*, Yu Katsuyama1,*,{dagger}, Kayo Arima1, Allison Baxter1, Tetsuya Koide1, Jihwan Song2, Roshantha A. S. Chandraratna3 and Bruce Blumberg1,{ddagger}

1 Department of Developmental and Cell Biology, University of California, Irvine, CA 92697-2300, USA
2 Laboratory of Stem Cell Biology, Cell & Gene Therapy Research Institute, Pochon CHA University College of Medicine, Seoul 135-081, Korea
3 Retinoid Research, Departments of Chemistry and Biology, Allergan, Irvine, CA 92623, USA

{ddagger} Author for correspondence (e-mail: blumberg{at}uci.edu)

Accepted 17 February 2004

Anteroposterior (AP) patterning of the developing CNS is crucial for both regional specification and the timing of neurogenesis. Several important factors are involved in AP patterning, including members of the WNT and FGF growth factor families, retinoic acid receptors, and HOX genes. We have examined the interactions between FGF and retinoic signaling pathways. Blockade of FGF signaling downregulates the expression of members of the RAR signaling pathway, RAR{alpha}, RALDH2 and CYP26. Overexpression of a constitutively active RAR{alpha}2 rescues the effects of FGF blockade on the expression of XCAD3 and HOXB9. This suggests that RAR{alpha}2 is required as a downstream target of FGF signaling for the posterior expression of XCAD3 and HOXB9. Surprisingly, we found that posterior expression of FGFR1 and FGFR4 was dependent on the expression of RAR{alpha}2. Anterior expression was also altered with FGFR1 expression being lost, whereas FGFR4 expression was expanded beyond its normal expression domain. RAR{alpha}2 is required for the expression of XCAD3 and HOXB9, and for the ability of XCAD3 to induce HOXB9 expression. We conclude that RAR{alpha}2 is required at multiple points in the posteriorization pathway, suggesting that correct AP neural patterning depends on a series of mutually interactive feedback loops among FGFs, RARs and HOX genes.

Key words: Retinoic acid, FGF, Xenopus, XCAD3


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