ZFIN ID: ZDB-PUB-181031-6
Altered bone growth dynamics prefigure craniosynostosis in a zebrafish model of Saethre-Chotzen syndrome
Teng, C.S., Ting, M.C., Farmer, D.T., Brockop, M., Maxson, R.E., Crump, J.G.
Date: 2018
Source: eLIFE   7: (Journal)
Registered Authors: Crump, Gage DeKoeyer
Keywords: Saethre-Chotzen Syndrome, Tcf12, Twist1, coronal suture, craniosynostosis, developmental biology, mouse, regenerative medicine, skull bones, stem cells, zebrafish
MeSH Terms:
  • Acrocephalosyndactylia/genetics*
  • Acrocephalosyndactylia/pathology
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors/genetics*
  • Bone Development
  • Craniosynostoses/genetics*
  • Craniosynostoses/pathology
  • Disease Models, Animal
  • Gene Expression Regulation, Developmental
  • Gene Knockout Techniques
  • Humans
  • Mice
  • Mutation
  • Neural Crest/growth & development
  • Neural Crest/pathology
  • Osteogenesis/genetics
  • Twist-Related Protein 1/genetics*
  • Zebrafish/genetics
PubMed: 30375332 Full text @ Elife
Cranial sutures separate the skull bones and house stem cells for bone growth and repair. In Saethre-Chotzen syndrome, mutations in TCF12 or TWIST1 ablate a specific suture, the coronal. This suture forms at a neural-crest/mesoderm interface in mammals and a mesoderm/mesoderm interface in zebrafish. Despite this difference, we show that combinatorial loss of TCF12 and TWIST1 homologs in zebrafish also results in specific loss of the coronal suture. Sequential bone staining reveals an initial, directional acceleration of bone production in the mutant skull, with subsequent localized stalling of bone growth prefiguring coronal suture loss. Mouse genetics further reveal requirements for Twist1 and Tcf12 in both the frontal and parietal bones for suture patency, and to maintain putative progenitors in the coronal region. These findings reveal conservation of coronal suture formation despite evolutionary shifts in embryonic origins, and suggest that the coronal suture might be especially susceptible to imbalances in progenitor maintenance and osteoblast differentiation.