Face off against ROS: Tcof1/Treacle safeguards neuroepithelial cells and progenitor neural crest cells from oxidative stress during craniofacial development

Dev Growth Differ. 2016 Sep;58(7):577-85. doi: 10.1111/dgd.12305. Epub 2016 Aug 2.


One-third of all congenital birth defects affect the head and face, and most craniofacial anomalies are considered to arise through defects in the development of cranial neural crest cells. Cranial neural crest cells give rise to the majority of craniofacial bones, cartilages and connective tissues. Therefore, understanding the events that control normal cranial neural crest and subsequent craniofacial development is important for elucidating the pathogenetic mechanisms of craniofacial anomalies and for the exploring potential therapeutic avenues for their prevention. Treacher Collins syndrome (TCS) is a congenital disorder characterized by severe craniofacial anomalies. An animal model of TCS, generated through mutation of Tcof1, the mouse (Mus musculus) homologue of the gene primarily mutated in association with TCS in humans, has recently revealed significant insights into the pathogenesis of TCS. Apoptotic elimination of neuroepithelial cells including neural crest cells is the primary cause of craniofacial defects in Tcof1 mutant embryos. However, our understanding of the mechanisms that induce tissue-specific apoptosis remains incomplete. In this review, we describe recent advances in our understanding of the pathogenesis TCS. Furthermore, we discuss the role of Tcof1 in normal embryonic development, the correlation between genetic and environmental factors on the severity of craniofacial abnormalities, and the prospect for prenatal prevention of craniofacial anomalies.

Keywords: DNA damage response/repair; Tcof1; craniofacial; neural crest cells; reactive oxygen species.

Publication types

  • Review

MeSH terms

  • Animals
  • Craniofacial Abnormalities / etiology
  • Craniofacial Abnormalities / pathology
  • Disease Models, Animal
  • Face / embryology*
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Neural Crest / cytology
  • Neural Crest / drug effects
  • Neural Stem Cells / physiology*
  • Neuroepithelial Cells / cytology
  • Neuroepithelial Cells / drug effects
  • Neuroepithelial Cells / physiology*
  • Nuclear Proteins / physiology*
  • Oxidative Stress / physiology*
  • Phosphoproteins / physiology*
  • Pregnancy
  • Reactive Oxygen Species / adverse effects*
  • Reactive Oxygen Species / pharmacology
  • Skull / embryology*


  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • Reactive Oxygen Species
  • Tcof1 protein, mouse