Research Biographies

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PROFESSOR IAN JACKSON

Medical and Developmental Genetics

Head of Medical and Developmental Genetics (Joint with Veronica van Heyningen)


Ian Jackson

Contact Details

E-mail address: ian.jackson@hgu.mrc.ac.uk
Telephone: +44 (0)131 332 2471 (extension 4003)
Direct Dial +44 (0)131 467 8409
Fax: +44 (0)131 467 8456
Address: Medical Research Council
Human Genetics Unit
Western General Hospital
Crewe Road
Edinburgh EH4 2XU
Research Programme 1: Molecular Genetics and
Development of Melanocytes
Research Programme 2: Genetic Models of Human Disease

 

Research Areas

Molecular Genetics and Development of Melanocytes

Melanocytes, the cells which produce melanin pigment in skin and hair, are an excellent system for understanding fundamental principles of developmental and cell biology. These cells arise in the neural crest and begin to migrate as melanoblasts through the developing dermis. They subsequently cross to the epidermis and ultimately become localised on the dermal-epidermal junction in the skin or within hair follicles. Once at their final site they begin to synthesis melanin and transfer it as granules to neighbouring keratinocytes. Mouse coat colour genetics has been studied for over 100 years, and provides a rich source of mutations that affect many aspects of melanocyte development and function. The genes underlying many of these mutations have now been identified. Those mutations that affect early development are often in genes that encode cell surface receptors, their ligands, or transcription factors. Mutations that affect later function of melanocytes are found in a range of genes, including those for receptors and ligands, but also encoding enzymes, structural proteins and proteins involved in organelle biosynthesis.

Genetic Models for Human Disease

Genome sequencing has revealed that the entire gene complement of the human genome appears to be surprisingly small. Nevertheless, there are still more than 20,000 genes, the vast majority of which do not have a function ascribed to them. The mouse genome has virtually the same gene content as the human genome, and these are found in the same order as in humans over quite large distances. The mouse genome is an excellent model for the human genome, and mouse genetics offers an opportunity to elucidate gene function by studying mutations in those genes. In addition these mutant animals are models for human diseases and help dissect the disease processes. We use chemical mutagenesis to produce random mutations and analyse the mice to identify mutant phenotype and subsequently find the mutated gene. We collaborate with MRC Mammalian Genetics Unit to discover genes involved in eye development and function. We also have screened for mutations resulting in embryonic defects.

 

Key/Selected Publications

  • Mill, P.; Lee, A.W.; Fukata, Y.; Tsutsumi, R.; Fukata, M.; Keighren, M.; Porter, R.M.; McKie, L.; Smyth, I. and Jackson, I.J. Palmitoylation regulates epidermal homeostasis and hair follicle differentiation. PLoS Genet. 5(11):e1000748, 2009 PubMed Abstract
  • Webb, T.R.; Cross, S.H.; McKie, L.; Edgar, R.; Vizor, L.; Harrison, J.; Peters, J. and Jackson, I.J. Diphthamide modification of eEF2 requires a J-domain protein and is essential for normal development. J Cell Sci 121(19):3140-3145, 2008 PubMed Abstract
  • Jackson, I.J.; Budd, P.S.; Keighren, M. and Mckie, L. Humanized MC1R transgenic mice reveal human specific receptor function. Human Molecular Genetics 16(19):2341-2348, 2007
    PubMed Abstract
  • Hart, A.; W, McKie, L.; Morgan, J.E.; Gautier, P.; West, K.; Jackson, I.J. and Cross, S.H. Genotype-phenotype correlation for mouse Pde6b mutations. Investigative Ophthalmology and Visual Science 46(9):3443-3450, 2005 PubMed Abstract
  • Van Agtmael, T.; Schlötzer-Schrehardt, U.; McKie, L.; Brownstein, D.G.; Lee, A.W.; Cross, S.H. ; Sado, Y.; Mullins, J.J.; Pöshl, E. and Jackson, I.J. Dominant mutations of Col4a1 result in basement membrane defects which lead to anterior segment defects and glomerupathy Human Molecular Genetics 14(21):3161-3168, 2005 PubMed Abstract
  • Cross, S.H.;,Morgan, J.E.; Pattyn, A.;West, K.; cKie, L.; lan Hart, A.; Thaung, C.; Brunet, J-F. and Jackson, I.J. Haploinsufficiency for Phox2b in mice causes dilated pupils and atrophy of the ciliary ganglion: mechanistic insights into human congenital central hypoventilation syndrome
    Human Molecular Genetics     13(14):1433-1439, 2004 PubMed Abstract
  • Smyth, I.; Du, X.; Taylor, M.S.; Justice, M.J.; Beutler, B. and Jackson, I.J. The extracellular matrix gene Frem 1 is essential for the normal adhesion of the embryonic epidermis.
    PNAS 101(37):13560-13565, 2004 PubMed Abstract
  • Wilkie, A.L.; Jordan, S.A.; Sharpe, J.A.; Price, D.J. and Jackson, I.J. Widespread tangential dispersion and extensive cell death during early neurogenesis in the mouse neocortex Developmental Biology 267(1):109-118, 2004 PubMed Abstract
  • Mouse Genome Sequencing Consortium Initial Sequencing and comparative analysis of the mouse genome. Nature 420:520-562, 2002 PubMed Abstract
  • Thaung, C.; West, K.; Clark, B.J.; Morgan, J.E.; Arnold, K.; McKie, L.; Nolan, P.N.; Peters, J.; Hunter, A.J.; Brown, S.D.M.; Jackson, I.J. and Cross, S.H. Novel ENU-induced eye mutations in the mouse – models for human eye disease Human Molecular Genetics 11(7):755-767, 2002 PubMed Abstract
  • Wilkie, A.L.; Jordan, S.A. and Jackson, I.J. Melanoblast Distribution in Mosaic and Chimaeric Mouse Embryos - Coat Colour Patterns Revisited. Development 129:3349-3357, 2002 PubMed Abstract
  • Healy, E.; Jordan, S.A.; Budd, P.S.; Suffolk, R.; Rees, J. and Jackson, I.J. Functional variation of MC1R alleles from red-haired individuals. Human Molecular Genetics 10(21):2397-2402, 2001
    PubMed Abstract
  • Jordan, S.A. and Jackson, I.J. MGF (KIT Ligand) is a chemokinetic factor for melanoblast migration into hair follicles. Developmental Biology 225:424-436, 2000 PubMed Abstract

 

Recent Publications

  • Mort, R.L.; Hay, L. and Jackson, I.J. Ex-vivo live imaging of melanoblast migration in embryonic mouse skin. Pigment Cell Melanoma Res e-pub Jan 7, 2010 PubMed Abstract
  • Church, D.M.; Goodstadt, L..... and the Mouse Genome Sequencing Consortium (Jackson, I.J.) Lineage-Specific Biology Revealed by a Finished Genome Assembly of the Mouse. PLoS Biol. 7(5):e1000112, 2009 PubMed Abstract
  • Lang, B.; Zhao, L.; Cai, L.; McKie, L.; Forrester, J.V.; McCaig, C.D.; Jackson, I.J. and Shen, S. GABAergic amacrine cells and visual function are reduced in PAC1 transgenic mice.
    Neuropharmacology 58(1):215-225, 2009 PubMed Abstract
  • Mengel-From, J.; Wong, T.H.; Morling, N.; Rees, J.L. and Jackson, I.J. Genetic determinants of hair and eye colour in the Scottish and Danish populations BMC Genet. 10(1):88, 2009
    PubMed Abstract
  • Mill, P.; Lee, A.W.; Fukata, Y.; Tsutsumi, R.; Fukata, M.; Keighren, M.; Porter, R.M.; McKie, L.; Smyth, I. and Jackson, I.J. Palmitoylation regulates epidermal homeostasis and hair follicle differentiation. PLoS Genet. 5(11):e1000748, 2009 PubMed Abstract
  • Gautier, P.; Naranjo-Golborne, C.; Taylor, M. S.; Jackson, I. J. and Smyth, I. Expression of the fras1/frem gene family during zebrafish development and fin morphogenesis. Developmental Dynamics 237(11):3295-3304. 2008 PubMed Abstract
  • Richardson, J.; Lundegaard, P.R.; Porteous, D.J.; Jackson, I.J. and Patton, E.E. Mc1r-Pathway Regulation of Zebrafish Melanosome Dispersion. Zebrafish. 5(4):289-295, 2008 PubMed Abstract
  • Webb, T.R.; Cross, S.H.; McKie, L.; Edgar, R.; Vizor, L.; Harrison, J.; Peters, J. and Jackson, I.J. Diphthamide modification of eEF2 requires a J-domain protein and is essential for normal development. J Cell Sci 121(19):3140-3145, 2008 PubMed Abstract
  • Dorin, J.R. and Jackson, I.J. Genetics. Beta-defensin repertoire expands. Science 318(5855): 1395, 2007 PubMed Abstract
  • Jackson, I.J.; Budd, P.S.; Keighren, M. and McKie, L. Humanized MC1R transgenic mice reveal human specific receptor function. Hum Mol Genet 16(19):2341-2348, 2007 PubMed Abstract
  • Hart, A.W.; Morgan, J.E.; Schneider, J.; West, K.; McKie, L.; Bhattacharya, S.; Jackson, I.J. and Cross, S.H. Cardiac malformations and midline skeletal defects in mice lacking filamin A.
    Hum Mol Genet     15(16):2457-2467, 2006 PubMed Abstract
  • Jackson, I.J. Identifying the genes causing human diversity. Eur J Hum Genet 14:978-980, 2006
    PubMed Abstract
  • Logan, D.W.; Burn, S.F. and Jackson, I.J. Regulation of pigmentation in zebrafish melanophores. Pigment Cell Res 19(3):206-213, 2006 PubMed Abstract
  • Smyth, I.M.; Wilming, L.; Lee, A.W.; Taylor, M.S.; Gautier, P.; Barlow, K.; Wallis, J.; Martin, S.; Glithero, R.; Phillimore, B.; Pelan, S.; Andrew, R.; Holt, K.; Taylor, R.; McLaren, S.; Burton, J.; Bailey, J.; Sims, S.; Squares, J.; Plumb, B.; Joy, A.; Gibson, R.; Gilbert, J.; Hart, E.; Laird, G.; Loveland, J.; Mudge, J.; Steward, C.; Swarbreck, D.; Harrow, J.; North, P.; Leaves, N.; Greystrong, J.; Coppola, M.; Manjunath, S.; Campbell, M.; Smith, M.; Strachan, G.; Tofts, C.; Boal, E.; Cobley, V.; Hunter, G.; Kimberley, C.; Thomas, D.; Cave-Berry, L.; Weston, P.; Marc, R.M.; White, S.; Edgar, R.; Cross, S.H.; Irvani, M.; Hummerich, H.; Simpson, E.H.; Johnson, D.; Hunsicker, P.R.; Little, P.F.R.; Hubbard, T.; Campbell, R.D.; Rogers, J. and Jackson, I.J. Genomic anatomy of the Tyrp1 (brown) deletion complex. PNAS 103(10):3704-3709, 2006 PubMed Abstract
  • Takemoto, Y.; Keighren, M.; Jackson, I.J. and Yamamoto, H. Genomic localization of a Dct-LacZ transgene locus: a simple assay for transgene status. Pigment Cell Res 19:644-645, 2006
    PubMed Abstract
  • Wells, D.J.; Playle, L.C.; Enser, W.E.; Flecknell, P.A.; Gardiner, M.A.; Holland, J.; Howard, B.R.; Hubrecht, R.; Humphreys, K.R.; Jackson, I.J.; Lane, N.; Maconochie, M.; Mason, G.; Morton, D.B.; Raymond, R.; Robinson, V.; Smith, J.A. and Watt, N. Assessing the welfare of genetically altered mice. Lab Anim 40(2):111-114, 2006 PubMed Abstract