Professor Mike Dixon
Research
Facial malformations are among the most common and distressing birth defects affecting man. Although the causes of such problems are complex, analysis of these conditions provides opportunities to identify the underlying genetic factors, to unravel the processes contributing to normal facial development, and to analyse how these are disrupted in birth defects.
Michael Dixon’s research group is playing a central role in analysing the complex pathways that underlie development of face by integrating the techniques of human genetics and developmental biology. The group has identified a number of different genes that are important in facial development. Recently, in collaboration with colleagues in the USA, Michael’s group has shown that a common form of cleft lip and palate, which causes problems with eating, hearing and speech, results from problems in a protein called interferon regulatory factor 6 (IRF6).
The group has subsequently shown that IRF6, working together with other proteins, is involved in ensuring that different parts of the face fuse together correctly during development. The results of on-going research are helping scientists and clinicians to understand how the face develops correctly. These advances have already impacted directly on the clinical management of affected individuals and their families and, in the longer term, may help to inform the design of treatments for cleft lip and cleft palate.
Michael Dixon’s research group is playing a central role in analysing the complex pathways that underlie development of face by integrating the techniques of human genetics and developmental biology. The group has identified a number of different genes that are important in facial development. Recently, in collaboration with colleagues in the USA, Michael’s group has shown that a common form of cleft lip and palate, which causes problems with eating, hearing and speech, results from problems in a protein called interferon regulatory factor 6 (IRF6).
The group has subsequently shown that IRF6, working together with other proteins, is involved in ensuring that different parts of the face fuse together correctly during development. The results of on-going research are helping scientists and clinicians to understand how the face develops correctly. These advances have already impacted directly on the clinical management of affected individuals and their families and, in the longer term, may help to inform the design of treatments for cleft lip and cleft palate.
Biography
Michael initially trained as a dentist at the University of Manchester, obtaining his BDS in 1983. Subsequently, Michael completed a PhD in developmental biology at Manchester in 1988, thereafter undertaking post-doctoral training in human genetics at Saint Mary’s Hospital, London. Michael is currently Professor of Dental Genetics at the University of Manchester with research interests in normal and abnormal facial development with particular emphasis on cleft lip and cleft palate.
Michael’s research group has played a central role in the identification of the genetic mutations underlying a number of human facial malformation syndromes including Treacher Collins syndrome, Papillon-Lefevre syndrome, Van der Woude/popliteal pterygium syndrome, amelogenesis imperfecta, and dentine dysplasia. This research is funded by major grants from Wellcome Trust, the Medical Research Council and the National Institute for Dental and Craniofacial Research, USA.
Michael’s research has been recognised by the award of several national and international prizes including the prestigious International Association for Dental Research Craniofacial Biology Research Award, 2001. In 2003, Michael was awarded the Fellowship in Dental Surgery by election, from the Royal College of Surgeons of England. Michael takes an active interest in communicating research findings to patient groups
Michael’s research group has played a central role in the identification of the genetic mutations underlying a number of human facial malformation syndromes including Treacher Collins syndrome, Papillon-Lefevre syndrome, Van der Woude/popliteal pterygium syndrome, amelogenesis imperfecta, and dentine dysplasia. This research is funded by major grants from Wellcome Trust, the Medical Research Council and the National Institute for Dental and Craniofacial Research, USA.
Michael’s research has been recognised by the award of several national and international prizes including the prestigious International Association for Dental Research Craniofacial Biology Research Award, 2001. In 2003, Michael was awarded the Fellowship in Dental Surgery by election, from the Royal College of Surgeons of England. Michael takes an active interest in communicating research findings to patient groups
Selected publications
2012
- Barlow, A., Dixon, J., Dixon, M. & Trainor, P (2012). Balancing neural crest cell intrinsic processes with those of the microenvironment in Tcof1 haploinsufficient mice enables complete enteric nervous system formation. Hum Mol Genet, 21(8), 1782-93. eScholarID:159894 | PMID:22228097 | DOI:10.1093/hmg/ddr611
- Blackburn, J., Ohazama, A., Kawasaki, K., Otsuka-Tanaka, Y., Liu, B., Honda, K., Rountree, R., Hu, Y., Kawasaki, M., Birchmeier, W., Schmidt-Ullrich, R., Kinoshita, A., Schutte, B., Hammond, N., Dixon, M. & Sharpe, P (2012). The role of Irf6 in tooth epithelial invagination. Dev Biol, 365(1), 61-70. eScholarID:159898 | PMID:22366192 | DOI:10.1016/j.ydbio.2012.02.009
- Ferone, G., Thomason, H., Antonini, D., De Rosa, L., Hu, B., Gemei, M., Zhou, H., Ambrosio, R., Rice, D., Acampora, D., van Bokhoven, H., Del Vecchio, L., Koster, M., Tadini, G., Spencer-Dene, B., Dixon, M., Dixon, J. & Missero, C (2012). Mutant p63 causes defective expansion of ectodermal progenitor cells and impaired FGF signalling in AEC syndrome. EMBO Mol Med, 4(3), 192-205. eScholarID:159902 | PMID:22247000 | DOI:10.1002/emmm.201100199
- Hammond, N., Headon, D. & Dixon, M (2012). The Cell Cycle Regulator Protein 14-3-3σ Is Essential for Hair Follicle Integrity and Epidermal Homeostasis. J Invest Dermatol, eScholarID:159899 | PMID:22377760 | DOI:10.1038/jid.2012.27
- Mitchell, K., O'Sullivan, J., Missero, C., Blair, E., Richardson, R., Anderson, B., Antonini, D., Murray, J., Shanske, A., Schutte, B., Romano, R., Sinha, S., Bhaskar, S., Black, G., Dixon, J. & Dixon, M (2012). Exome sequence identifies RIPK4 as the Bartsocas-Papas syndrome locus. Am J Hum Genet, 90(1), 69-75. eScholarID:159896 | PMID:22197488 | DOI:10.1016/j.ajhg.2011.11.013
- Sakai, D., Dixon, J., Dixon, M. & Trainor, P (2012). Mammalian neurogenesis requires treacle-plk1 for precise control of spindle orientation, mitotic progression, and maintenance of neural progenitor cells. PLoS Genet, 8(3), e1002566. eScholarID:159897 | PMID:22479190 | DOI:10.1371/journal.pgen.1002566
2011
- Brookes, S., Kingswell, N., Barron, M., Dixon, M. & Kirkham, J (2011). Is the 32-kDa fragment the functional enamelin unit in all species? Eur J Oral Sci, 119 Suppl 1, 345-50. eScholarID:159895 | PMID:22243266 | DOI:10.1111/j.1600-0722.2011.00869.x
- Dauwerse, J., Dixon, J., Seland, S., Ruivenkamp, C., van Haeringen, A., Hoefsloot, L., Peters, D., Boers, A., Daumer-Haas, C., Maiwald, R., Zweier, C., Kerr, B., Cobo, A., Toral, J., Hoogeboom, A., Lohmann, D., Hehr, U., Dixon, M., Breuning, M. & Wieczorek, D (2011). Mutations in genes encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome. Nat Genet, 43(1), 20-2. eScholarID:133439 | PMID:21131976 | DOI:10.1038/ng.724
- Dixon, M., Marazita, M., Beaty, T. & Murray, J (2011). Cleft lip and palate: understanding genetic and environmental influences. Nat Rev Genet, 12(3), 167-78. eScholarID:133440 | PMID:21331089 | DOI:10.1038/nrg2933
- Ferretti, E., Li, B., Zewdu, R., Wells, V., Hebert, J., Karner, C., Anderson, M., Williams, T., Dixon, J., Dixon, M., Depew, M. & Selleri, L (2011). A conserved Pbx-Wnt-p63-Irf6 regulatory module controls face morphogenesis by promoting epithelial apoptosis. Dev Cell, 21(4), 627-41. eScholarID:149789 | PMID:21982646 | DOI:10.1016/j.devcel.2011.08.005
- O'Sullivan, J., Bitu, C., Daly, S., Urquhart, J., Barron, M., Bhaskar, S., Martelli-Júnior, H., dos Santos Neto, P., Mansilla, M., Murray, J., Coletta, R., Black, G. & Dixon, M (2011). Whole-Exome sequencing identifies FAM20A mutations as a cause of amelogenesis imperfecta and gingival hyperplasia syndrome. Am J Hum Genet, 88(5), 616-20. eScholarID:133441 | PMID:21549343 | DOI:10.1016/j.ajhg.2011.04.005
- Restivo, G., Nguyen, B., Dziunycz, P., Ristorcelli, E., Ryan, R., Özuysal, Ö., Di Piazza, M., Radtke, F., Dixon, M., Hofbauer, G., Lefort, K. & Dotto, G (2011). IRF6 is a mediator of Notch pro-differentiation and tumour suppressive function in keratinocytes. EMBO J, 30(22), 4571-85. eScholarID:149790 | PMID:21909072 | DOI:10.1038/emboj.2011.325
- Swartz, M., Sheehan-Rooney, K., Dixon, M. & Eberhart, J (2011). Examination of a palatogenic gene program in zebrafish. Dev Dyn, 240(9), 2204-20. eScholarID:149791 | PMID:22016187 | DOI:10.1002/dvdy.22713
2010
- Barron, M., Brookes, S., Kirkham, J., Shore, R., Hunt, C., Mironov, A., Kingswell, N., Maycock, J., Shuttleworth, C. & Dixon, M (2010). A mutation in the mouse Amelx tri-tyrosyl domain results in impaired secretion of amelogenin and phenocopies human X-linked amelogenesis imperfecta. Hum Mol Genet, 19(7), 1230-47. eScholarID:80175 | PMID:20067920 | DOI:10.1093/hmg/ddq001
- Richter, C., Amin, S., Linden, J., Dixon, J., Dixon, M. & Tucker, A (2010). Defects in middle ear cavitation cause conductive hearing loss in the Tcof1 mutant mouse. Hum Mol Genet, 19(8), 1551-60. eScholarID:80174 | PMID:20106873 | DOI:10.1093/hmg/ddq028
- Sheehan-Rooney K, Pálinkášová B, Eberhart JK, Dixon MJ. (2010). A cross-species analysis of Satb2 expression suggests deep conservation across vertebrate lineages. Developmental Dynamics, 239, 3481. eScholarID:114081 | DOI:10.1002/dvdy.22483
- Thomason, H., Zhou, H., Kouwenhoven, E., Dotto, G., Restivo, G., Nguyen, B., Little, H., Dixon, M., van Bokhoven, H. & Dixon, J (2010). Cooperation between the transcription factors p63 and IRF6 is essential to prevent cleft palate in mice. J Clin Invest, eScholarID:80173 | PMID:20424327 | DOI:10.1172/JCI40266
2009
- Ferreira de Lima, R, Hoper, S, Ghassibe, M, Cooper, M, Rorick, N, Kondo, S, Katz, L, Marazita, M, Compton, J, Bale, S, Hehr, U, Dixon, MJ, Daack-Hirsch, S, Boute, O, Bayet, B, Revencu, N, Verellen-Dumoulin, C, Vikkula, M, Richieri-Costa, A, Moretti-Ferreira, D, Murray, J, Schutte, B. (2009). Prevalence and nonrandom distribution of exonic mutations in interferon regulatory factor 6 in 307 families with Van der Woude syndrome and 37 families with popliteal pterygium syndrome. Genet Med, eScholarID:1d18887 | DOI:10.1097/GIM.0b013e318197a49a
- Heath J, Langton AK, Hammond NL, Overbeek PA, Dixon MJ, Headon DJ. (2009). Hair Follicles Are Required for Optimal Growth during Lateral Skin Expansion. J Invest Dermatol, eScholarID:1d21705 | DOI:10.1038/jid.2009.102
- Heath, J., Langton, A., Hammond, N., Overbeek, P., Dixon, M. & Headon, D (2009). Hair follicles are required for optimal growth during lateral skin expansion. J Invest Dermatol, 129(10), 2358-64. eScholarID:80178 | PMID:19387480 | DOI:10.1038/jid.2009.102
- Little HJ, Rorick NK, Su LI, Baldock C, Malhotra S, Jowitt T, Gakhar L, Subramanian R, Schutte BC, Dixon MJ, Shore P. (2009). Missense mutations that cause Van der Woude syndrome and popliteal pterygium syndrome affect the DNA-binding and transcriptional activation functions of IRF6. Human molecular genetics, 18(3), eScholarID:1c8099 | PMID:19036739 | DOI:10.1093/hmg/ddn381
- Mossey, P., Little, J., Munger, R., Dixon, M. & Shaw, W (2009). Cleft lip and palate. Lancet, 374(9703), 1773-85. eScholarID:80176 | PMID:19747722 | DOI:10.1016/S0140-6736(09)60695-4
- Richardson, R., Dixon, J., Jiang, R. & Dixon, M (2009). Integration of IRF6 and Jagged2 signalling is essential for controlling palatal adhesion and fusion competence. Hum Mol Genet, 18(14), 2632-42. eScholarID:80177 | PMID:19439425 | DOI:10.1093/hmg/ddp201
- Thomason HA, Dixon MJ. (2009). Craniofacial defects and cleft lip and palate. Encyclopaedia of Life Sciences, DOI: 10.1002/9780470015902.a0020915]. eScholarID:114111
- Trainor, P., Dixon, J. & Dixon, M (2009). Treacher Collins syndrome: etiology, pathogenesis and prevention. Eur J Hum Genet, 17(3), 275-83. eScholarID:80179 | PMID:19107148 | DOI:10.1038/ejhg.2008.221
2008
- Dixon J, Dixon MJ. (2008). Treacle and Treacher Collins syndrome. In Epstein CJ, Erickson RP, Wynshaw-Boris A (Ed.), Inborn Errors of Development. (pp. 1033-1141). Oxford: Oxford University Press. eScholarID:114124
- Richardson RJ, Dixon MJ. (2008). GJA1, connexin 43 and oculodentodigital syndrome. In Epstein CJ, Erickson RP, Wynshaw-Boris A (Ed.), Inborn Errors of Development. (pp. 1483-1489). Oxford: Oxford University Press. eScholarID:114131
- Schutte BC, Dixon MJ, Murray JC. (2008). Interferon Regulatory Factor 6 (IRF6) is causal in Van der Woude and popliteal pterygium syndromes and contributes to the risk for non-syndromic cleft lip and palate. In Epstein CJ, Erickson RP, Wynshaw-Boris A (Ed.), Inborn Errors of Development. (pp. 1069-1072). Oxford: Oxford University Press. eScholarID:114114
- Barron MJ, Brookes SJ, Draper CE, Garrod D, Kirkham J, Shore RC, Dixon MJ. (2008). The cell adhesion molecule nectin-1 is critical for normal enamel formation in mice. Human molecular genetics, 17(22), eScholarID:1c8205 | PMID:18703497 | DOI:10.1093/hmg/ddn243
- Barron MJ, McDonnell ST, Mackie I, Dixon MJ. (2008). Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia. Orphanet journal of rare diseases, 3, 31. eScholarID:1c8203 | PMID:19021896 | DOI:10.1186/1750-1172-3-31
- Barron, M., McDonnell, S., Mackie, I. & Dixon, M (2008). Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia. Orphanet J Rare Dis, 3, 31. eScholarID:80180 | PMID:19021896 | DOI:10.1186/1750-1172-3-31
- Fenwick A, Richardson RJ, Butterworth J, Barron MJ, Dixon MJ. (2008). Novel mutations in GJA1 cause oculodentodigital syndrome. Journal of dental research, 87(11), 1021-6. eScholarID:1c8204 | PMID:18946008 | DOI:10.1177/154405910808701108
- Jones NC, Lynn ML, Gaudenz K, Sakai D, Aoto K, Rey JP, Glynn EF, Ellington L, Du C, Dixon J, Dixon MJ, Trainor PA. (2008). Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function. Nature medicine, 14(2), eScholarID:1c8207 | PMID:18246078 | DOI:10.1038/nm1725
- Mou C, Thomason HA, Willan PM, Clowes C, Harris WE, Drew CF, Dixon J, Dixon MJ, Headon DJ. (2008). Enhanced EDAR signaling alters multiple fiber characteristics to produce the East Asian hair form. Human Mutation, In press, eScholarID:1c7405 | DOI:10.1002/humu.20795
- Thomason HA, Dixon MJ, Dixon J. (2008). Facial clefting in Tp63 deficient mice results from altered Bmp4, Fgf8 and Shh signaling. Developmental biology, 321(1), 273-82. eScholarID:1c8206 | PMID:18634775 | DOI:10.1016/j.ydbio.2008.06.030
2002
- H. Rajpar, M. Koch, Davies RM, Mellody KK, Kielty CM, Dixon MJ. (2002). Mutation of the signal peptide region of the bicistronic gene DSPP affects translocation to the endoplasmic reticulum and results in defective dentine biomineralization. Human Molecular Genetics, 11, 2559-2565. eScholarID:1d24249 | DOI:10.1093/hmg/11.21.2559
- S. Kondo, B. Schutte, R. Richardson, B Bjork, A. Knight, Y. Watanabe, E. Howard, R. Ferreira de Lima, S. Daack-Hirsch, A. Sander, D McDonald, E. Zackai, E. Lammer, A Aylsworth, Ardinger, H, A. Lidral, B. Prober, L. Moreno, M Arcos-Burgos, C. Valencia, C. Houdayer, M. Bahuau, Moretti-Ferreira, D, A. Richieri, Dixon, MJ, J. Murray. (2002). Mutations in IRF6 cause Van der Woude and Popliteal pterygium syndromes. Nature Genetics, 32, 285-. eScholarID:1d24251 | DOI:10.1038/ng985
2001
- Rajpar M.H, Harley K, Laing C, Davies RM, Dixon MJ. (2001). Mutation of the gene encoding the enamel-specific protein, enamelin, causes autosomal dominant amelogenesis imperfecta. Hum Mol Genet, 10, 1673-1677. eScholarID:1d1700 | DOI:10.1093/hmg/10.16.1673