Activin type I receptor (ALK4) is a switch for the dual action of the activin/ALK4 pathway: promoting mesodermal lineage and inhibiting neural fate
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| Year of publication | 2012 |
| Type | Conference abstract |
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| Description | During embryogenesis, the Activin/Nodal pathway plays a crucial role in lineage decision. In vivo studies showed that different concentrations of Activin elicit distinct responses from Xenopus animal caps, ultimately producing a range of mesodermal fates. Nodal-/- mice fail to form both the mesoderm and the definitive endoderm, but show precocious neural differentiation, suggesting that the Activin/Nodal pathway promotes mesodermal lineage and inhibits neural fate decision. This is corroborated by a series of studies in vitro. Blockage of Activin signalling has been shown to promote neural fate in human ES cells and in mouse ES cells (our unpublished data). What molecular mechanism underlies the dual role of the Activn/Nodal pathway is not clear. We have discovered that protein tyrosine phosphatase 1B (Ptp1B) acts as a novel partner of the Activin/Alk4 pathway to select between mesodermal or neural fates. We employed human and mouse embryonic stem (ES) cell-differentiation model to investigate the function of the Activin/Alk4 pathway in the early fate decision. We found that the treatment of Activin at the different stages of ES cell differentiation exhibit diverse influences in cell-type derivatives. Inhibition of the Activin pathway at different time windows also shows a stage-dependent fate adaptation. A downstream factor of this pathway, Ptp1B, has been identified to interact with Alk4, which in turn governs Activin-directed fate decision in combination with p-Smad2/3 signalling. |