Skull bone fusion (craniosynostosis) and repair are paradigms to understand the basic functions of stem/progenitor cells and how they can be harnessed for treatment of disease. They are thought to be regulated by primary cilia in response to mechanical pressure. We have used gene-editing to create an entirely novel series of mouse mutants in the gene Ift80 whereby we can genetically ‘dial’ the level of ciliary function up or down. We will use these models to investigate the role of different types of stem cells in skull formation and maintenance.
(*denotes publications from the host lab):
*1) Seda et al. An FDA-Approved Drug Screen for Compounds Influencing Craniofacial Skeletal Development and Craniosynostosis. Mol Syndromol. 10:98-114.
*2) Jenkins et al. RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity. Am J Hum Genet. 80:1162-70.
*3) Beales et al. IFT80, which encodes a conserved intraflagellar transport protein, is mutated in Jeune asphyxiating thoracic dystrophy. Nat Genet. 39:727-9.
4) Zhao H, Feng J, Ho TV, Grimes W, Urata M, Chai Y. The suture provides a niche for mesenchymal stem cells of craniofacial bones. Nat Cell Biol. 17:386-96.
5) Dalagiorgou et al. Mechanical stimulation of polycystin-1 induces human osteoblastic gene expression via potentiation of the calcineurin/NFAT signaling axis. Cell Mol Life Sci. 70:167-80.