The old and new face of craniofacial research: How animal models inform human craniofacial genetic and clinical data

Dev Biol. 2016 Jul 15;415(2):171-187. doi: 10.1016/j.ydbio.2016.01.017. Epub 2016 Jan 22.


The craniofacial skeletal structures that comprise the human head develop from multiple tissues that converge to form the bones and cartilage of the face. Because of their complex development and morphogenesis, many human birth defects arise due to disruptions in these cellular populations. Thus, determining how these structures normally develop is vital if we are to gain a deeper understanding of craniofacial birth defects and devise treatment and prevention options. In this review, we will focus on how animal model systems have been used historically and in an ongoing context to enhance our understanding of human craniofacial development. We do this by first highlighting "animal to man" approaches; that is, how animal models are being utilized to understand fundamental mechanisms of craniofacial development. We discuss emerging technologies, including high throughput sequencing and genome editing, and new animal repository resources, and how their application can revolutionize the future of animal models in craniofacial research. Secondly, we highlight "man to animal" approaches, including the current use of animal models to test the function of candidate human disease variants. Specifically, we outline a common workflow deployed after discovery of a potentially disease causing variant based on a select set of recent examples in which human mutations are investigated in vivo using animal models. Collectively, these topics will provide a pipeline for the use of animal models in understanding human craniofacial development and disease for clinical geneticist and basic researchers alike.

Keywords: Animal model systems; Craniofacial; Genetic screens; Human clinical genetics; Neural crest.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chick Embryo
  • Craniofacial Abnormalities / embryology
  • Craniofacial Abnormalities / genetics*
  • Databases, Factual
  • Disease Models, Animal*
  • Enhancer Elements, Genetic
  • Forecasting
  • Gene Expression Regulation, Developmental / genetics
  • Genetic Association Studies
  • Head / embryology
  • Humans
  • Maxillofacial Development / genetics*
  • Mice
  • Mutagenesis
  • Mutation
  • Neural Crest / embryology
  • Species Specificity
  • Xenopus
  • Zebrafish
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / physiology


  • Zebrafish Proteins