2012
Activin type I receptor (ALK4) is a switch for the dual action of the activin/ALK4 pathway: promoting mesodermal lineage and inhibiting neural fate
MATULKA, Kamil; Lin HSUAN-HWAI; Hana HŘÍBKOVÁ; Petr DVOŘÁK; Yuh-Man SUN et al.Základní údaje
Originální název
Activin type I receptor (ALK4) is a switch for the dual action of the activin/ALK4 pathway: promoting mesodermal lineage and inhibiting neural fate
Autoři
Vydání
ISSCR 10th Annual Meeting, 13.-.16.6.2012, Yokohama, Japonsko, 2012
Další údaje
Jazyk
angličtina
Typ výsledku
Konferenční abstrakt
Stát vydavatele
Japonsko
Utajení
není předmětem státního či obchodního tajemství
Označené pro přenos do RIV
Ne
Organizační jednotka
Lékařská fakulta
Příznaky
Mezinárodní význam
Změněno: 17. 9. 2012 17:15, Mgr. Martina Vráblíková
Anotace
V originále
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 Blockage of Activin signalling has been shown to promote neural fate in human ES cells and in mouse ES cells (our unpublished data).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.