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Investigating the Role of Primary Cilia in Cranial Stem/Progenitor Cell Development and Craniosynostosis

Dagan Jenkins 3 Research Image

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.

Disciplines and Techniques
Project supervisor/s
Dr. Dagan Jenkins
Dagan is interested in investigating the pathogenesis and treatment of skeletal ciliopathies.
University College London
Professor Martin Knight
Martin is interested in 'mechanobiology' or how living cells and tissues respond to physical forces.
Queen Mary University of London
References
An FDA-Approved Drug Screen for Compounds Influencing Craniofacial Skeletal Development and Craniosynostosis
Seda et al.
Mol Syndromol. 10:98-114
unknown
RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity
Jenkins et al.
Am J Hum Genet. 80:1162-70
unknown
IFT80, which encodes a conserved intraflagellar transport protein, is mutated in Jeune asphyxiating thoracic dystrophy
Beales et al.
Nat Genet. 39:727-9
unknown
The suture provides a niche for mesenchymal stem cells of craniofacial bones.
Zhao H, Feng J, Ho TV, Grimes W, Urata M, Chai Y.
Nat Cell Biol. 17:386-96
unknown
Mechanical stimulation of polycystin-1 induces human osteoblastic gene expression via potentiation of the calcineurin/NFAT signaling axis
Dalagiorgou et al.
Cell Mol Life Sci. 70:167-80
unknown