Craniofacial traits determined by neural crest cells-restricted expression of Dlx5/6: probing the origin of matching functional jaws

During gnathostome development, lower and upper jaws derive from the first pharyngeal arch (PA1), a complex structure constituted by Neural Crest Cells (NCCs), mesodermal, ectodermal and endodermal cell populations. Lower jaw (mandibular) identity depends on endothelin-1 (Edn1)-mediated activation of Dlx5/6 in PA1 NCCs. Transient expression of Dlx5/6 in ectodermal cells is also necessary for correct jaw morphogenesis. Here we inactivate or overexpress Dlx5/6 specifically in NCCs to determine the morphogenetic impact of their expression in these cells. Invalidation of Dlx5/6 in NCCs (NCCΔDlx5/6) generates severely hypomorphic lower jaws that present typical maxillary traits. Reciprocally, forced expression of Dlx5 in maxillary NCCs (NCCDlx5), provokes the transformation of the upper jaw into a structure that presents distinct mandibular characters. Therefore, similarly to Edn1-signalling mutants, the NCCΔDlx5/6 jaw transformation engenders an asymmetric mouth that is strikingly different from the symmetric jaws obtained after constitutive Dlx5/6 inactivation. Our data demonstrate that: 1) Dlx5/6 expression in NCCs is necessary and sufficient to specify mandibular identity; 2) these same genes must also be regulated in other cell types to generate functional matching jaws capable to support mastication. These finding are critical to understand the developmental and evolutionary origin of distinct and synergic anatomical structures.