Endogenous and ectopic expression of noggin suggests a conserved mechanism for regulation of BMP function during limb...

The gene noggin, originally cloned in Xenopus, encodes a secreted factor expressed in the Spemann organizer, where it functions to oppose the ventralizing influence of bone morphogenetic proteins (BMPs). Noggin protein acts by binding directly to BMPs, thereby preventing them from interacting with their receptors. Here we describe the pattern of expression of the chicken noggin gene during somite and limb development, two tissues in which BMPs have been postulated to play essential patterning roles. We find that noggin is expressed in dynamic restricted patterns consistent with an important role in the modulation of BMP signaling. Using a replication competent retrovirus we have ectopically expressed noggin in developing somitic and limb bud mesoderm and observed phenotypes consistent with complete block of BMP activity. This includes suppression of lateral somite differentiation and, in the limb, complete inhibition of chondrogenesis and local suppression of programmed cell death. In addition, we find that ectopic noggin expression in the limb has no effect on anteroposterior limb pattern, suggesting that BMPs are unlikely to play a significant role in this process. Taken together,, our results indicate that noggin is a key regulator of vertebrate limb and somite patterning and suggest that the antagonistic Noggin-BMP interaction is a widely used mechanism to modulate BMP signaling during multiple inductive events in vertebrate embryogenesis.