Similarly hhex expression in hepatoblasts is FGF dependent in zebrafish embryos and chick explants. Our results are in general agreement with these studies. we also found that FGF signaling promoted liver and lung and repressed pancreas. However we did not find any evi dence supporting a dose requirement for liver versus lung selleckbio induction in Xenopus, although we cannot totally rule out this mechanism. We also did not find discrete short periods in development when liver versus lung fate was induced. Rather our data support a duration model where prolonged FGF signaling is required to specify both liver and lung lineages, with the lung seeming to require a longer duration of FGF activity.

Different Inhibitors,Modulators,Libraries dura tions of FGF signaling are important in the development of other systems as well, for instance, in lens epithelial cells it has been shown that low doses of FGF signaling promote proliferation while high doses of FGF promote fiber Inhibitors,Modulators,Libraries differentiation. We also postulate that the spatial requirement for FGF signaling in vivo is also likely to be important factor in regulating the duration of exposure to a FGF signal. We observed that in some FGF inhibited embryos the re sidual liver gene expression was immediately next to the cardiac mesoderm, suggesting liver gene ex pression was only induced in the cells closest to a source of FGF. It is important to point out that our experiments do not formally demonstrate Inhibitors,Modulators,Libraries that the mesoderm alone is the source of the FGF ligands. evidence from chick and Xenopus embryos shows the endoderm also expresses FGF ligands and thus autocrine signaling within the endoderm could be involved.

Inhibitors,Modulators,Libraries Inhibitors,Modulators,Libraries Our data indicate that both the MEK and PI3K branches of the FGF response contribute to lung and liver induction. Inhibition of either branch resulted in intermediate phenotypes compared to FGFRi, while combining MEKi and PI3Ki caused a dramatic loss of mature liver and lung markers recapitulating the FGFRi treatment. Our data also indicate that the PI3K activity is important http://www.selleckchem.com/products/crenolanib-cp-868596.html for cell survival and proliferation, and some of this activity appears to be FGF independent, consist ent with a report that pAkt signaling has an anti apoptotic role in Xenopus stomach/pancreas develop ment. Our in vivo findings that both MEK and PI3K are involved in liver and lung specification differ some what from explant studies of the mouse liver, where the MEK branch is important for hepatic gene expression while the PI3K branch is important for explant growth.