BMP signaling participates in the regulation of Shh's domain of expression during limb development

Abstract

The secreted factor Sonic hedgehog (Shh) plays a critical role during limb development controlling patterning in the anterior‐posterior axis. It is expressed by a group of cells at the posterior border of the bud that constitute the Zone of polarizing activity (ZPA). Interestingly, the domain of Shh expression in the posterior border of the bud, once activated, remains of a similar size during further development despite the fact that cell lineage analysis has demonstrated that Shh descendants extend beyond the expression domain of Shh expression. This indicates the existence of mechanisms controlling the number and location of Shh–expressing cells. Here we show that BMP signaling participates in the control of Shh domain of expression by negatively regulating Shh expression and that this function is not mediated by interfering with the known positive regulation exerted by FGFs from the Apical ectodermal ridge or by WNT7A signaling from the dorsal ectoderm. We also show that this BMP function is achieved indirectly requiring protein synthesis and that the proposed mechanism based on Shh induction of cell‐death is mediated by BMP signaling. Supported by grant BFU2005–09309–CO2–01 from Spanish Ministry of Education and Science.