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Gnathostome jaws derive from the first pharyngeal arch (PA1), a complex structure constituted by Neural Crest Cells (NCCs), mesodermal, ectodermal and endodermal cells. Here, to determine the regionalized morphogenetic impact of  Dlx5/ 6 expression, we specifically target their inactivation or overexpression to NCCs. NCC-specific  Dlx5/6  inactivation ( NCC   ∆Dlx5/6  ) generates severely hypomorphic lower jaws that present typical maxillary traits. Therefore, differently from  Dlx5/6  null-embryos, the upper and the lower jaws of  NCC   ∆Dlx5/6   mice present a different size. Reciprocally, forced  Dlx5  expression in maxillary NCCs provokes the appearance of distinct mandibular characters in the upper jaw. We conclude that: (1)  Dlx5/6  activation in NCCs invariably determines lower jaw identity; (2) the morphogenetic processes that generate functional matching jaws depend on the harmonization of  Dlx5/6  expression in NCCs and in distinct ectodermal territories. The co-evolution of synergistic opposing jaws requires the coordination of distinct regulatory pathways involving the same transcription factors in distant embryonic territories.

Probing the origin of matching functional jaws: roles of Dlx5/6 in cranial neural crest cells