During limb development, the zone of polarizing activity (ZPA) in the limb bud controls the bud's growth and patterning by producing the signalling molecule sonic hedgehog (SHH). Any alteration in Shh expression affects limb development but, although the factors that activate and maintain Shh expression have been identified, what restricts Shhexpression to the ZPA is unclear. Now, on , Bastida and colleagues reveal the central role that bone morphogenetic protein (BMP) plays in restricting Shh expression during posterior limb development in mice and chicks. The researchers show that BMP indirectly downregulates Shh expression by interfering with the FGF and Wnt signalling pathways that maintain Shh expression. Furthermore, they report,because SHH positively regulates the expression of BMP genes, a negative-feedback loop operates between BMPs and SHH to confine Shhexpression to the ZPA. Finally, BMP gene expression is positively regulated by FGF signalling and negatively regulated by an auto-regulatory loop. Together,these results reveal the complex crosstalk between signalling pathways that ensures accurate limb development.
