A major feature of Saethre-Chotzen syndrome is coronal craniosynostosis, the fusion of the frontal and parietal bones at the coronal suture. It is caused by heterozygous loss-of-function mutations in either of the basic HLH transcription factors TWIST1 and TCF12. While compound heterozygous Tcf12; Twist1 mice display severe coronal synostosis, the individual role of Tcf12 had remained unexplored. Here we show that Tcf12 controls several key processes in calvarial development, including the rate of frontal and parietal bone growth, and the boundary between sutural and osteogenic cells. Genetic analysis supports an embryonic requirement for Tcf12 in suture formation, as combined deletion of Tcf12 in embryonic neural crest and mesoderm, but not in postnatal suture mesenchyme, disrupts the coronal suture. We also detect asymmetric distribution of mesenchymal cells on opposing sides of the wild-type frontal and parietal bones, which prefigures later bone overlap at the sutures. In Tcf12 mutants, reduced asymmetry is associated with bones meeting end-on-end, possibly contributing to synostosis. Our results support embryonic requirements of Tcf12 in proper formation of the overlapping coronal suture.
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RESEARCH ARTICLE|
08 December 2021
Embryonic requirements for Tcf12 in the development of the mouse coronal suture
Man-chun Ting
,
Man-chun Ting
2
Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033
, USA
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D'Juan T. Farmer,
D'Juan T. Farmer
1
Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033
, USA
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Camilla S. Teng
,
Camilla S. Teng
1
Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033
, USA
2
Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033
, USA
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Jinzhi He,
Jinzhi He
3
Center for Craniofacial Molecular Biology, School of Dentistry, University of Southern California, Los Angeles, CA 90033
, USA
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Yang Chai
,
Yang Chai
3
Center for Craniofacial Molecular Biology, School of Dentistry, University of Southern California, Los Angeles, CA 90033
, USA
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J. Gage Crump
,
J. Gage Crump
*
1
Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033
, USA
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Robert E. Maxson, Jr.
Robert E. Maxson, Jr.
*
1
Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033
, USA
2
Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033
, USA
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Man-chun Ting
2
Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033
, USA
D'Juan T. Farmer
1
Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033
, USA
Camilla S. Teng
1
Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033
, USA
2
Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033
, USA
Jinzhi He
3
Center for Craniofacial Molecular Biology, School of Dentistry, University of Southern California, Los Angeles, CA 90033
, USA
Yang Chai
3
Center for Craniofacial Molecular Biology, School of Dentistry, University of Southern California, Los Angeles, CA 90033
, USA
J. Gage Crump
*
1
Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033
, USA
Robert E. Maxson, Jr.
*
1
Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033
, USA
2
Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033
, USA
Received:
02 Mar 2021
Accepted:
22 Nov 2021
Online ISSN: 1477-9129
Print ISSN: 0950-1991
Funding Group:
- Award Group:
- Funder(s): National Institutes of Health
- Award Id(s): R01DE026339
- Funder(s):
Development dev.199575.
Article history
Received:
02 Mar 2021
Accepted:
22 Nov 2021
Currently Viewing Accepted Manuscript - Newer Version Available
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Citation
Man-chun Ting, D'Juan T. Farmer, Camilla S. Teng, Jinzhi He, Yang Chai, J. Gage Crump, Robert E. Maxson; Embryonic requirements for Tcf12 in the development of the mouse coronal suture. Development 2021; dev.199575. doi: https://doi.org/10.1242/dev.199575
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