File:Model retinoic acid extracellular signal-regulated kinase and Wnt pathway interactions.jpg

Model retinoic acid extracellular signal-regulated kinase and Wnt pathway interactions

A. Interaction between retinoic acid (RA) and the extracellular signal-regulated kinase (ERK) pathway during promoted neural specification. FGF receptor tyrosine kinase inhibitor SU5402 and MEK1/2 inhibitors PD184352 and PD0325901, respectively suppresses neural differentiation of ESCs. In RA-treated cultures, PD184352, PD0325901 and RARα-selective antagonist Ro 41–5253 could inhibit the neural specification of ESCs, while SU5402 shows weak neural inhibition effect. RA probably enhances ERK phosphorylation via MEK1/2 or its upstream but not in a manner that is dependent on FGF signaling, and activated ERK1/2 mediates phosphorylation of the MAPK sites of Smad1 (pSmad1MAPK), which inhibits the inhibitory function of the bone morphogenetic proteins (BMPs)-Smad1 pathway on neural differentiation. Blockade of RA signaling might affect the activation of the upstream of ERK1/2, which leads to failure of neural specification of ESCs even with the stimulation of FGF signaling.

B. Possible roles of Wnt signaling in RA-promoted neural differentiation. RA promotes neural specification probably by up-regulating Sfrp2, which inhibits the Wnt-β-catenin anti-neural pathway. Upon adding LiCl or CHIR99021, which stimulates the β-catenin signaling and/or BMP signaling through inhibition of GSK3, the suppression effects on neural specification of β-catenin pathway can be passed down even with the stimuli of RA. RA also may promote neural differentiation by up-regulating RAR, which may decrease β-catenin/LEF/TCF mediated transactivation. There exists a possibility that RA may suppress the inhibition effects on neural differentiation of Wnt-β-catenin pathway by sequestration of β-catenin. pSmad1GSK3 indicates phosphorylation of the GSK3 sites of Smad1.

extracellular signal-regulated kinase (ERK)

Links: Developmental Signals - Retinoic acid | Developmental Signals - Wnt

Reference

<pubmed>19642999</pubmed>

Lu et al. BMC Cell Biology 2009 10:57 doi:10.1186/1471-2121-10-57

Copyright

© 2009 Lu et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Original file name: Figure 6. 1471-2121-10-57-6-l.jpg

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