Previous studies have implied that the specification of osteoblasts - the cells that secrete bone matrix - involves Hedgehog (Hh) and canonical Wnt signalling. On , Rodda and McMahon test this idea directly by genetic manipulation within osteoblast progenitors and find that these pathways have sequential roles in osteoblast specification. By conditionally removingβ-catenin in specific cell types, they show that canonical Wnt signalling is necessary to stop osteoblast precursors from becoming chondrocytes (cells that produce cartilage). Conversely, using a stabilised form ofβ-catenin, they found that too much canonical Wnt signalling causes the overproliferation of osteoblast precursors and excessive mineralisation. They have also found that osteoblast specification requires only transient Hh signalling, and that Hh is not required during the formation of mature osteoblasts. The authors go on to discuss how Hh and Wnt might sequentially regulate osteoblast differentiation, speculating that the programmes of chondrocytes and osteoblast development are regulated by a balance between Sox9 and β-catenin.
