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

Miki Shimizu,Camille De Lombares,Eglantine Heude,Giovanni Levi,Yumiko Kawamura,Lindsey Marshall,Youichiro Wada,Taro Kitazawa,Hiroki Kurihara,Yukiko Kurihara,Nicolas Narboux-Nême,Yorick Gitton,Gladys Alfama,Anastasia Fontaine,Hiroki Higashiyama

doi:10.1038/s41598-018-33207-2

Abstract

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.

Highlights

Gnathostome jaws derive from the first pharyngeal arch (PA1), a complex structure constituted by Neural Crest Cells (NCCs), mesodermal, ectodermal and endodermal cells
Given the difference between the lower jaw morphology obtained in Edn1/endothelin receptor type-A (Ednra) mutants and Dlx5/6 mutants, these findings suggest that the Edn1-dependent activation of Dlx5/6 in NCCs is necessary to specify mandibular identity, but is insufficient to generate a normal lower jaw morphology[17,20,22,23,30]
The lower jaw of contemporary species is constituted by two mobile dentary bones that form around an early rod-like Meckelian cartilage and converge towards the centre where they fuse at the mandibular symphysis

Summary

Introduction

Gnathostome jaws derive from the first pharyngeal arch (PA1), a complex structure constituted by Neural Crest Cells (NCCs), mesodermal, ectodermal and endodermal cells. Loss of Edn[1] and/or endothelin receptor type-A (Ednra)[20,21] result in the transformation of the lower jaw into a structure presenting major morphological hallmarks of an upper jaw such as absence of MC, zygomatic arch-like structures and vibrissae. These observations indicate that Edn[1] signalling plays a major role in the specification of lower jaw identity[22,23]. It appears that Edn[1] drives lower jaw development through a calmodulin-CamKII-histone deacetylase cascade that de-represses Mef2c, which transactivates Dlx5/6 expression[25,26]

Methods

Results

Conclusion