Early steps in limb patterning and chondrogenesis.

The interplay of a number of signalling molecules coordinates growth and patterning of the early embryonic vertebrate limb along the three axes. An unresolved question is how this information translates into proper positioning and patterning of the skeletal elements. More is known about how these elements develop. Cells first form precartilaginous condensations and then subsequently differentiate into chondrocytes. This provides a cartilage template that will ultimately be ossified to give rise to the bony skeleton. Several studies support a role for the bone morphogenetic proteins (BMPs) as extracellular signals that regulate early steps of limb chondrogenesis (cartilage formation). However, they have not clarified the step(s) at which BMPs act, and no genetic evidence is available to date. Here, we have used a retroviral vector to misexpress the BMP antagonist Noggin in the embryonic chick limb. We find that BMP signalling is necessary for the formation of precartilaginous condensations, their differentiation into chondrocytes, and for maintenance of chondrogenesis. These results also indicate that Noggin could be clinically useful to treat diseases involving ectopic cartilage formation.