Multiple points of interaction between retinoic acid and FGF signaling during embryonic axis formation
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 α, RALDH2 and CYP26 .
Overexpression of a constitutively active RAR α 2
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
RAR α 2 . 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.
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