TY - JOUR
T1 - Multiple points of interaction between retinoic acid and FGF signaling during embryonic axis formation
AU - Shiotsugu, Jason
AU - Katsuyama, Yu
AU - Arima, Kayo
AU - Baxter, Allison
AU - Koide, Tetsuya
AU - Song, Jihwan
AU - Chandraratna, Roshantha A.S.
AU - Blumberg, Bruce
PY - 2004/6
Y1 - 2004/6
N2 - 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, RARα, RALDH2 and CYP26. Overexpression of a constitutively active RARα2 rescues the effects of FGF blockade on the expression of XCAD3 and HOXB9. This suggests that RARα2 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 RARα2. Anterior expression was also altered with FGFR1 expression being lost, whereas FGFR4 expression was expanded beyond its normal expression domain. RARα2 is required for the expression of XCAD3 and HOXB9, and for the ability of XCAD3 to induce HOXB9 expression. We conclude that RARα2 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.
AB - 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, RARα, RALDH2 and CYP26. Overexpression of a constitutively active RARα2 rescues the effects of FGF blockade on the expression of XCAD3 and HOXB9. This suggests that RARα2 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 RARα2. Anterior expression was also altered with FGFR1 expression being lost, whereas FGFR4 expression was expanded beyond its normal expression domain. RARα2 is required for the expression of XCAD3 and HOXB9, and for the ability of XCAD3 to induce HOXB9 expression. We conclude that RARα2 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.
KW - FGF
KW - Retinoic acid
KW - XCAD3
KW - Xenopus
UR - http://www.scopus.com/inward/record.url?scp=3042776327&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3042776327&partnerID=8YFLogxK
U2 - 10.1242/dev.01129
DO - 10.1242/dev.01129
M3 - Review article
C2 - 15128657
AN - SCOPUS:3042776327
VL - 131
SP - 2653
EP - 2667
JO - Journal of Embryology and Experimental Morphology
JF - Journal of Embryology and Experimental Morphology
SN - 0950-1991
IS - 11
ER -