Specific inactivation of Twist1 in the mandibular arch neural crest cells affects the development of the ramus and reveals interactions with hand2

Dev Dyn. 2012 May;241(5):924-40. doi: 10.1002/dvdy.23776. Epub 2012 Mar 29.


Background: The basic helix-loop-helix (bHLH) transcription factor Twist1 fulfills an essential function in neural crest cell formation, migration, and survival and is associated with the craniosynostic Saethre-Chotzen syndrome in humans. However, its functions during mandibular development, when it may interact with other bHLH transcription factors like Hand2, are unknown because mice homozygous for the Twist1 null mutation die in early embryogenesis. To determine the role of Twist1 during mandibular development, we used the Hand2-Cre transgene to conditionally inactivate the gene in the neural crest cells populating the mandibular pharyngeal arch.

Results: The mutant mice exhibited a spectrum of craniofacial anomalies, including mandibular hypoplasia, altered middle ear development, and cleft palate. It appears that Twist1 is essential for the survival of the neural crest cells involved in the development of the mandibular ramal elements. Twist1 plays a role in molar development and cusp formation by participating in the reciprocal signaling needed for the formation of the enamel knot. This gene is also needed to control the ossification of the mandible, a redundant role shared with Hand2.

Conclusion: Twist1, along with Hand2, is essential for the proximodistal patterning and development of the mandible and ossification.

Publication types

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

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Branchial Region / abnormalities
  • Branchial Region / metabolism*
  • Craniofacial Abnormalities / genetics*
  • Craniofacial Abnormalities / metabolism
  • Gene Expression Regulation, Developmental
  • Mandible / abnormalities
  • Mandible / metabolism*
  • Mice
  • Mice, Transgenic
  • Neural Crest / cytology*
  • Neural Crest / metabolism
  • Neurons / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Organogenesis / genetics
  • Twist-Related Protein 1 / genetics*
  • Twist-Related Protein 1 / metabolism


  • Basic Helix-Loop-Helix Transcription Factors
  • Hand2 protein, mouse
  • Nuclear Proteins
  • Twist-Related Protein 1
  • Twist1 protein, mouse