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An endothelin-1 switch specifies maxillomandibular identity.

Takahiro Sato1, Yukiko Kurihara, Rieko Asai

  • 1Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Proceedings of the National Academy of Sciences of the United States of America
|November 20, 2008
PubMed
Summary
This summary is machine-generated.

Endothelin-1 (Edn1) signaling can transform upper jaw structures into lower jaw components. This discovery in cephalic neural crest cells (CNCCs) reveals sequential specification and developmental plasticity in jaw formation.

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Area of Science:

  • Developmental biology
  • Evolutionary biology
  • Craniofacial development

Background:

  • Articulated jaws are conserved in jawed vertebrates (gnathostomes).
  • Epithelial-mesenchymal interactions in the first pharyngeal arch (PA1) guide cephalic neural crest cells (CNCCs) to form jaw skeletal elements.
  • The endothelin-1 (Edn1)/endothelin receptor type-A (Ednra) to Dlx5/6 to Hand2 pathway is crucial for lower jaw development.

Purpose of the Study:

  • To investigate the sufficiency of Edn1 signaling in jaw identity determination.
  • To explore the role of Ednra and Hand2 in craniofacial skeletal transformations.
  • To understand the developmental plasticity and specification of CNCCs within PA1.

Main Methods:

  • Constitutive activation of Ednra in vivo.
  • Misexpression of Hand2 within the Ednra domain.
  • Analysis of skeletal and neuromuscular remodeling in response to genetic manipulation.

Main Results:

  • Constitutive Ednra activation transformed maxillary arch structures into mandibular identity, resulting in duplicated Meckel's cartilage and four dentary bones.
  • Hand2 misexpression in the Ednra domain mimicked this transformation.
  • Skeletal changes were accompanied by significant neuromuscular remodeling.

Conclusions:

  • CNCCs are not equivalent after migration, suggesting sequential specification steps.
  • CNCCs within PA1 are competent to form both maxillary and mandibular structures.
  • Edn1 signaling acts as a crucial switch determining the morphogenetic program for jaw development.