Large parts of the craniofacial and pharyngeal skeleton derive from cranial neural crest cells (NCCs) that migrate from the edge of the dorsal neural tube(DNT) to populate the pharyngeal arches (PAs - a series of transient structures that contribute to head and neck formation) and the frontonasal process (which contributes to the forehead and nose). In this issue, two papers provide important new insights into the signalling events involved in this morphogenetic process.
On , Filippo Rijli, Denis Duboule and colleagues reveal that the first four PAs share a common NCC gene expression ground state. NCCs that contribute to individual PAs express distinct Hox gene combinations that determine PA-specific regional identities; for example, the NCCs that populate the first PA are Hox-negative. Previously, these authors have shown that the first and second PA NCCs in mice share a common Hox-free patterning programme. Now, they demonstrate that deleting the entire HoxA cluster in cranial NCCs leads to the partial homeotic transformation of the third and fourth PA towards a first PA identity. Amongst other effects, this results in the partial quadruplication of Meckel's jaw cartilage, an evolutionarily ancient structure from which the lower jaw and middle ear develop. These findings support the idea that all PAs are part of a single series of segmental structures, and invite the suggestion that the elaboration of regional identity in such structures on top of a shared gene expression ground state constitutes a general evolutionary strategy.
In their study, Hiromi Yanagisawa and colleagues turn to later NCC differentiation events in craniofacial bone development in mice, and report that endothelial signalling through the transcription factor Hand2 negatively regulates the differentiation of NCC-derived osteoblasts in PAs (see ). The authors demonstrate that a decrease in PA-specific Hand2 expression leads to accelerated osteoblast differentiation associated with the increased and ectopic expression of the transcription factor Runx2, a master regulator of bone differentiation. Based on these and other findings, the authors propose that a vertebrate-specific domain of Hand2 interacts directly with the DNA-binding domain of Runx2 to negatively regulate its activity.
