Figure 6.
Fmn1 represses Smad phosphorylation through Bmp signaling. (A) Embryo fibroblasts derived from wild-type and Fmn1Pro/Pro mice were induced with increasing concentrations of Bmp4, indicated by solid inclining triangle. Smad1, 5, 8 phosphorylation, P-Smad as a response to Bmp signaling, was assessed by western blot analysis. Cell extracts were additionally blotted with antibodies to unphosphorylated Smad and α-tubulin (MT), lower panels. (B) Two hundred and ninety-three cells transfected with an HA-tagged fragment of Fmn1 or an empty vector were induced with increasing concentrations of Bmp4. P-Smad, Smad and HA-Fmn1 were analyzed by western blot. (C) Depiction of the role of Fmn1 in regulation of Bmp. This model indicated that Fmn1 acts as a repressor of Bmp signaling. This in turn leads to an increase in Msx expression, a decrease in Fgf4/8 and consequently, a decrease in Shh. Additionally, this explains the upregulation of Gremlin that was observed in the developing limb bud. Gremlin acts as an antagonist of Bmp which might lead to subsequent downregulation of Bmp activity.