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.
|Original language||English (US)|
|Number of pages||17|
|State||Published - Jul 15 2016|
Bibliographical noteFunding Information:
The authors would like to thank Dr. Tamim Shaikh for helpful discussions of human craniofacial syndromes and help with Fig. 1 . Work in the Artinger lab is supported by the National Institute of Dental and Craniofacial Research (R01DE024034), work in the Williams lab is supported by the National Institute of Dental and Craniofacial Research (U01DE024429) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (1R01HD081562), and EVO, in the Williams lab, is supported by Fellowship F32DE02370 from the National Institute of Dental and Craniofacial Research, in part by a Cleft Palate Foundation Research Support Grant, and an American Association of Anatomists Postdoctoral Fellowship. Finally, we would also like to acknowledge the many pertinent studies by our colleagues that due to space constraints we were unable to cover in this manuscript.
Pearl et al. (2012) European Xenopus Resource Centre (EXRC) “The European Xenopus Resource Centre (EXRC) is funded by the Wellcome Trust, BBSRC and NC3Rs to support researchers using Xenopus models.” http://www.port.ac.uk/research/exrc/
© 2016 Elsevier Inc.
- Animal model systems
- Genetic screens
- Human clinical genetics
- Neural crest