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Understanding the basis of auriculocondylar syndrome: Insights from human, mouse and zebrafish genetic studies

Authors

  • David E. Clouthier,

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    • David E. Clouthier is an Associate Professor in the School of Dental Medicine at the University of Colorado Anschutz Medical Campus. His lab focuses on the regulation of neural crest cell patterning and facial morphogenesis, utilizing both mouse and zebrafish models.
  • Maria Rita Passos-Bueno,

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    • Maria Rita Passos-Bueno is a full professor in the Institute of Biosciences at University of São Paulo. Her lab is dedicated to the study of the genetic mechanisms of craniofacial syndromes and autism spectrum disorders.
  • Andre L.P. Tavares,

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    • Andre L.P. Tavares is a post-doctoral researcher in the School of Dental Medicine at the University of Colorado Anschutz Medical Campus. His research interests include embryonic patterning of the craniofacial complex and the basis of human facial dysmorphologies.
  • Stanislas Lyonnet,

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    • Stanislas Lyonnet and Jeanne Amiel are clinical geneticists at the Hôpital Necker-Enfants Malades. Their research interests are focused on the genetic causes of rare malformative syndromes, particularly those involving defects in neural crest cells.
  • Jeanne Amiel,

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    • Stanislas Lyonnet and Jeanne Amiel are clinical geneticists at the Hôpital Necker-Enfants Malades. Their research interests are focused on the genetic causes of rare malformative syndromes, particularly those involving defects in neural crest cells.
  • Christopher T. Gordon

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    • Christopher Gordon is a post-doctoral researcher at the Hôpital Necker-Enfants Malades. His research interests include craniofacial developmental biology and the genetic causes of human craniofacial disorders.

  • The authors have no conflict of interest to declare.

Correspondence to: David E. Clouthier, Ph.D., Department of Craniofacial Biology, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045. E-mail: david.clouthier@ucdenver.edu

Correspondence to: Christopher T. Gordon, Ph.D., INSERM U781, Tour Lavoisier 2eme etage, Hopital Necker-Enfants Malades, 149 rue de Sevres, Paris 75015, France. E-mail: chris.gordon@inserm.fr

Abstract

Among human birth defect syndromes, malformations affecting the face are perhaps the most striking due to cultural and psychological expectations of facial shape. One such syndrome is auriculocondylar syndrome (ACS), in which patients present with defects in ear and mandible development. Affected structures arise from cranial neural crest cells, a population of cells in the embryo that reside in the pharyngeal arches and give rise to most of the bone, cartilage and connective tissue of the face. Recent studies have found that most cases of ACS arise from defects in signaling molecules associated with the endothelin signaling pathway. Disruption of this signaling pathway in both mouse and zebrafish results in loss of identity of neural crest cells of the mandibular portion of the first pharyngeal arch and the subsequent repatterning of these cells, leading to homeosis of lower jaw structures into more maxillary-like structures. These findings illustrate the importance of endothelin signaling in normal human craniofacial development and illustrate how clinical and basic science approaches can coalesce to improve our understanding of the genetic basis of human birth defect syndromes. Further, understanding the genetic basis for ACS that lies outside of known endothelin signaling components may help elucidate unknown aspects critical to the establishment of neural crest cell patterning during facial morphogenesis. © 2013 Wiley Periodicals, Inc.

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