Defining the mechanism of limb regeneration: A potential novel role for BAMBI in mediating Fgf‐induced Shh up‐regulation

The mechanism used by Fgf to regulate Shh expression during limb development and regeneration is unknown. Elevated levels of BMP pathway associated genes (BMP7 and BAMBI) were identified by gene array analysis in stage 23 chick limbs during SHH up‐regulation by FGF2. To investigate the role of these BMP pathway members during Fgf‐induced regulation of Shh, we analyzed the expression time course of BMP7 and BAMBI following implantation of FGF2‐soaked beads into the posterior aspect of stage 23 chick wing buds. The chicks were harvested 3 – 24 hr after incubation and an in situ hybridization for BMP7 and BAMBI was performed. BMP7 expression was not elevated after 24 hr of FGF2 treatment (in contrast to gene array data), while FGF2‐induced BAMBI up‐regulation was validated. Furthermore, BAMBI expression was evident within 6 hr after FGF2 application. These results were unexpected. We anticipated that BMP7 would be up‐regulated, followed by its inhibitor, BAMBI. The up‐regulation of BAMBI without up‐regulation of BMP7 suggested an alternative role for BAMBI. Recent studies have demonstrated that BAMBI can act as a positive modulator of the Wnt/β‐catenin pathway, a pathway known to participate in Shh regulation. Our data suggests that BAMBI may play a novel role in Fgf‐induced Shh up‐regulation by modulating the Wnt/β‐catenin pathway. Grant Funding Source : Macpherson Society