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Transcriptional Control of Cranial Suture Development
Author(s) -
Maxson Robert,
Teng Camilla,
Ting Manchun,
Crump Gage
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.364.3
Subject(s) - craniosynostosis , cranial vault , skull , coronal suture , anatomy , biology , fibrous joint , zebrafish , medicine , microbiology and biotechnology , genetics , gene
The skull is a complex, exquisitely patterned structure with key roles in many aspects of vertebrate life, ranging from the acquisition of food to the support of the sense organs for hearing, smell, sight, and taste. During its development it must meet the dual challenges of protecting the brain and accommodating its growth. The flat bones at the top of the skull compose the skull vault, or calvaria. Between the bones are sutures, fibrous joints that allow the skull vault to flex during childbirth and act as a growth center in postnatal growth and homeostasis. A number of congenital disorders affect the development of the skull vault. Prominent among these is Saethre‐Chotzen syndrome is a disorder characterized by premature fusion of the bones of the skull vault (craniosynostosis) and facial irregularities. Heterozygous mutations in the basic helix‐loop‐helix (bHLH) transcription factor TWIST1 account for roughly 71% of Saethre‐Chotzen syndrome diagnoses. Recently, patients with Saethre‐Chotzen syndrome who do not carry TWIST1 mutations were found instead to have mutations in TCF12 , another bHLH gene. Suggesting an interaction between these genes, loss of Tcf12 enhances craniosynostosis in Twist1+/ − mice. Marker analysis in individual and compound Twist1 and Tcf12 mutants suggests that these two genes cooperatively control a set of downstream processes, including the specification of sutural cells as well as the boundary between osteogenic and non‐osteogenic cells at the coronal suture. To further explore the role of Twist1 and Tcf12 in suture development, we have developed a zebrafish model of suture development that appears to closely mimic mammalian sutures. Using TALEN‐mediated mutagenesis, we have generated null alleles for both zebrafish Twist1 homologs ( twist1a and twist1b ) and tcf12 . Remarkably, a portion of zebrafish doubly null for twist1b and tcf12 are adult viable yet display near complete loss of the coronal suture. Our data provide strong evidence for deep evolutionary homology of the coronal suture between fish and mammals, thus suggesting that the zebrafish will be a useful model for understanding craniosynostosis in humans. Support or Funding Information This work was supported by grants from the NIH (NIDCR) to RM, CT, and GC