Twist is required for establishment of the mouse coronal suture.
Cranial sutures are the growth centres of the skull, enabling expansion of the skull to accommodate rapid growth of the brain. Haploinsufficiency of the human TWIST gene function causes the craniosynostosis syndrome, Saethre-Chotzen syndrome (SCS), in which premature fusion of the coronal suture is a characteristic feature. Previous studies have indicated that Twist is expressed in the coronal suture during development, and therefore that it may play an important role in development and maintenance of the suture. The Twist-null mouse is lethal before the onset of osteogenesis, and the heterozygote exhibits coronal suture synostosis postnatally. In this study we investigated the function of Twist in the development of the mouse coronal suture, by inhibiting Twist synthesis using morpholino antisense oligonucleotides in calvarial organ culture. Decreased Twist production resulted in a narrow sutural space and fusion of bone domains within 48 h after the addition of the morpholino oligonucleotides. Proliferation activity in the sutural cells was decreased, and the expression of osteogenic marker genes such as Runx2 and Fgfr2 was up-regulated in the developing bone domain within 4 h. These results suggest that during establishment of the suture area, Twist is required for the regulation of sutural cell proliferation and osteoblast differentiation.
Yoshida
Toshiyuki
T
Department of Molecular Craniofacial Embryology, Graduate School, Tokyo Medical and Dental University, Japan.
Phylactou
Leonidas A
LA
Uney
James B
JB
Ishikawa
Isao
I
Eto
Kazuhiro
K
Iseki
Sachiko
S
D000168:Acrocephalosyndactylia / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002454:Cell Differentiation; D049109:Cell Proliferation; D003393:Cranial Sutures / Q000196:embryology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009924:Organ Culture Techniques; D010006:Osteoblasts / Q000166:cytology; D012886:Skull; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D051879:Twist-Related Protein 1
D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D014157:Transcription Factors; D051879:Twist-Related Protein 1