PROFESSOR IAN JACKSON
Medical and Developmental Genetics
Head of Medical and Developmental Genetics (Joint with David FitzPatrick)
|Telephone:||+44 (0)131 332 2471 (extension 4003)|
|Direct Dial||+44 (0)131 467 8409|
|Fax:||+44 (0)131 467 8456|
|Address:||MRC Human Genetics Unit MRC IGMM, University of Edinburgh 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|
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.
- 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
- 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
- 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
- Kinsler VA, Abu-Amero S, Budd P, Jackson IJ, Ring SM, Northstone K, Atherton DJ, Bulstrode NW, Stanier P, Hennekam RC, Sebire NJ, Moore GE, Healy E: Germline Melanocortin-1-Receptor Genotype Is Associated with Severity of Cutaneous Phenotype in Congenital Melanocytic Nevi: A Role for MC1R in Human Fetal Development
J Invest Dermatol 2012.
- Lindsay CR, Lawn S, Campbell AD, Faller WJ, Rambow F, Mort RL, Timpson P, Li A, Cammareri P, Ridgway RA, Morton JP, Doyle B, Hegarty S, Rafferty M, Murphy IG, McDermott EW, Sheahan K, Pedone K, Finn AJ, Groben PA, Thomas NE, Hao H, Carson C, Norman JC, Machesky LM, Gallagher WM, Jackson IJ, Van KL, Beermann F, Der C, Larue L, Welch HC, Ozanne BW, Sansom OJ: P-Rex1 is required for efficient melanoblast migration and melanoma metastasis
Nat Commun 2:555, 2011.PubMed Abstract
- Li A, Ma Y, Yu X, Mort RL, Lindsay CR, Stevenson D, Strathdee D, Insall RH, Chernoff J, Snapper SB, Jackson IJ, Larue L, Sansom OJ, Machesky LM: Rac1 Drives Melanoblast Organization during Mouse Development by Orchestrating Pseudopod- Driven Motility and Cell-Cycle Progression
Dev Cell 21: 722-734 2011.PubMed Abstract
- Keane TM, Goodstadt L, Danecek P, White MA, Wong K, Yalcin B, Heger A, Agam A, Slater G, Goodson M, Furlotte NA, Eskin E, Nellaker C, Whitley H, Cleak J, Janowitz D, Hernandez-Pliego P, Edwards A, Belgard TG, Oliver PL, McIntyre RE, Bhomra A, Nicod J, Gan X, Yuan W, van der Weyden L, Steward CA, Bala S, Stalker J, Mott R, Durbin R, Jackson IJ, Czechanski A, Guerra-Assuncao JA, Donahue LR, Reinholdt LG, Payseur BA, Ponting CP, Birney E, Flint J, Adams DJ: Mouse genomic variation and its effect on phenotypes and gene regulation. Nature 477(7364):289-294, 2011. PubMed Abstract
- Taylor KL, Lister JA, Zeng Z, Ishizaki H, Anderson C, Kelsh RN, Jackson IJ, Patton EE: Differentiated melanocyte cell division occurs in vivo and is promoted by mutations in Mitf
9. Development 138:3579-3589, 2011. PubMed Abstract
- Richardson J, Zeng Z, Ceol C, Mione M, Jackson IJ, Patton EE: A zebrafish model for nevus regeneration. Pigment Cell Melanoma Res 24:378-381, 2011. PubMed Abstract
- Rainger J, van BE, Ramsay JK, McKie L, Al-Gazali L, Pallotta R, Saponari A, Branney P, Fisher M, Morrison H, Bicknell L, Gautier P, Perry P, Sokhi K, Sexton D, Bardakjian TM, Schneider AS, Elcioglu N, Ozkinay F, Koenig R, Megarbane A, Semerci CN, Khan A, Zafar S, Hennekam R, Sousa SB, Ramos L, Garavelli L, Furga AS, Wischmeijer A, Jackson IJ, Gillessen-Kaesbach G, Brunner HG, Wieczorek D, van BH, Fitzpatrick DR: Loss of the BMP Antagonist, SMOC-1, Causes Ophthalmo-Acromelic (Waardenburg Anophthalmia) Syndrome in Humans and Mice. PLoS Genet 7(7):e1002114, 2011.
- Cross SH, McKie L, West K, Coghill EL, Favor J, Bhattacharya S, Brown SD, Jackson IJ: The Opdc missense mutation of Pax2 has a milder than loss-of-function phenotype. Hum Mol Genet 20(2):223-234, 2011. PubMed Abstract
- Mill P, Lockhart PJ, Fitzpatrick E, Mountford HS, Hall EA, Reijns MA, Keighren M, Bahlo M, Bromhead CJ, Budd P, Aftimos S, Delatycki MB, Savarirayan R, Jackson IJ, Amor DJ: Human and Mouse Mutations in WDR35 Cause Short-Rib Polydactyly Syndromes Due to Abnormal Ciliogenesis. Am J Hum Genet 88(4):508-515, 2011. PubMed Abstract
- van Agtmael, T.; Bailey, M.A.; Schlotzer-Schrehardt, U.; Craigie, E.; Jackson, I.J.; Brownstein, D.G.; Megson, I.L. and Mullins, J.J. Col4a1 mutation in mice causes defects in vascular function and low blood pressure associated with reduced red blood cell volume.
Hum.Mol.Genet. 19(6):1119-1128, 2010 PubMed Abstract
- Mort, R.L.; Hay, L. and Jackson, I.J. Ex-vivo live imaging of melanoblast migration in embryonic mouse skin. Pigment Cell Melanoma Res 23(2):229-301, 2010 PubMed Abstract