The Arkell Group - Early Mammalian Development

It's not birth, marriage, or death, but gastrulation which is truly the most important time in your life

Lewis Wolpert, 1992

Gastrulation is the process that converts a relatively undifferentiated group of cells into an embryo with easily recognisable structures. All adult form and function is dependent upon gastrulation and this is why it is truly the most important time in your life. We study the genetic mechanisms that control mammalian gastrulation and the consequences of incorrect gastrulation. Current research focuses on a group of transcription factors that control brain, heart, skin and skeletal development. We aim to understand the complex molecular processes by which these transcription factors interact with signal transduction pathways, chromatin, RNA and other proteins in order to orchestrate these important developmental processes

Ruth Arkell currently heads the Early Mammalian Development Laboratory. She completed her undergraduate studies at the University of Sydney (BSc, Hons) and commenced doctoral studies in Mouse Molecular Embryology in 1992 at Edinburgh University. These studies were completed at the Institute for Medical Research in London in 1996. In order to capitalize on the new opportunities which would arise once the mouse genome sequence was available she pursued postdoctoral research training (in London and Oxfordshire) in mouse functional genetics. In 2000 she was awarded a UK MRC Career Development Award and established a research group in Oxfordshire to study gene function during mouse gastrulation. In 2006 she was a Sylvia and Charles Viertel Senior Medical Fellowship recipient and moved her research to The Australian National University. In 2009 she was the recipient of the Australian and New Zealand Society for Cell and Developmental Biology Young Investigator Award. She continues to utilize embryology, cell biology and functional genetics to study the molecular and embryological basis of congenital defects that have their aetiology in gastrulation.

Publications

Selected publications

  • Barratt, K.S, Glanville-Jones, H.C. and Arkell, R.M. The Zic2 gene directs the formation and function of node cilia to control cardiac situs. Genesis 2014 Mar 2. doi: 10.1002/dvg.22767.
  • Arkell, R. M., Fossat, N., Tam, P. P. L. Wnt signalling in mouse gastrulation and anterior development: new players in the pathway and signal output.  2013  Curr Opin Genet Dev. 23(4):454-60.
  • Glanville-Jones, H.C., Woo, N., Arkell, R.M. Successful whole embryo culture with commercially available reagents. (2013)  Int J Dev Biol, 57(1):61-7.
  • Ahmed, J.N., Ali, R.G., Warr, N., Wilson, H.M., Bellchambers, H.M., Barratt, K.S., Thompson, A.J., and Arkell, R.M.  A Zic3 Transcript with a Premature Termination Codon Evades Nonsense Mediated Decay during Axis Formation.  (2013)  Dis Mod Mech. 6(3):755-67.
  • Houtmeyers, R., Souopgui, J., Tejpar, S., Arkell, R. The ZIC gene family encodes multi-functional proteins essential for patterning and morphogenesis.  (2013)  Cell Mol Life Sci. 70(20):3791-811.
  • Caruana, G., Farlie, P.G., Hart, A.H., Bagheri-Fam, S., Wallace, M.J., Dobbie, M.S., Gordon, C.T., Miller, K.A., Whittle, B., Abud, H.E., Arkell, R.M., Cole, T.J., Harley, V.R., Smyth, I.M., Bertram, J.F. Genome-Wide ENU Mutagenesis in Combination with High Density SNP Analysis and Exome Sequencing Provides Rapid Identification of Novel Mouse Models of Developmental Disease.  (2013)  PLoS One 2013;8(3):e55429..
  • Watkins-Chow, D. E., Cooke, J. Pidsley, R. Edwards, A. Slotkin, R. Leeds, K. E. Mullen, R., Baxter, L. L., Campbell, T. G., Salzer, M. C., Biondini, L., Gibney, G., Phan Dinh Tuy, F., Chelly, J., Morris, H. D., Riegler, J., Lythgoe, M. F., Arkell, R. M., Loreni, F., Flint, J., Pavan, W. J., Keays, D. A. Mutation of the Diamond-Blackfan anemia gene Rps7 in mouse results in morphological and neuroanatomical phenotypes.  (2013)  PLoS Genet. 9(1):e1003094.
  • Thomsen, N., Ali, R. G., Ahmed, J. N., Arkell, R. M. High Resolution Melt Analysis (HRMA); a Viable Alternative to Agarose Gel Electrophoresis for Mouse Genotyping.  (2012)  PLoS ONE 7(9): e45252.
  • Ali, R. G., Bellchambers, H., Arkell, R. M. Zinc fingers of the cerebellum (Zic): transcription factors and co-factors.  (2012) Int J Biochem Cell Biol. 44(11):2065-2068.
  • Arkell, R. M., Tam, P.P.L. Initiating head development in mouse embryos: integrating signalling and transcriptional activity.  (2012)  Open Biol. 2(3):120030.
  • Fossat, N., Jones, V., Khoo, P.L., Bogani, D., Hardy, A., Steiner, K., Mukhopadhyay, M., Westphal, H., Nolan, P.M., Arkell, R., Tam, P.P. Stringent requirement of a proper level of canonical WNT signalling activity for head formation in mouse embryo.  (2011)  Development 138(4):667-76
  • Mackenzie, F.E., Romero, R., Williams, D., Gillingwater, T., Hilton, H., Dick, J., Riddoch-Contreras, J., Wong, F., Ireson, L., Powles-Glover, N., Riley, G., Underhill, P., Hough, T., Arkell, R., Greensmith, L., Ribchester, R.R., Blanco, G. Upregulation of PKD1L2 provokes a complex neuromuscular disease in the mouse.  (2009)  Hum Mol Genet. 18(19):3553-3566.
  • Warr, N., Powles-Glover, N., Chappell, A., Robson, J., Norris, D.,  Arkell, R.M. Zic2-associated holoprosencephaly is caused by a transient defect in the organiser region during gastrulation.  (2008)  Hum Mol Genet. 17(19):2986-96.
  • Ybot-Gonzalez, P., Gaston-Massuet, C., Girdler, G., Klingensmith, J., Arkell, R., Greene, N.D.E. and Copp, A.J. Neural plate morphogenesis during mouse neurulation is regulated by antagonism of Bmp signaling.  (2007)  Development 134(17):3203-11.
  • Bogani, D., Willoughby, C., Davies, J., Kaur, K., Mirza, G., Paudyal, A., Haines, H., McKeone, R., Cadman, M., Pieles, G., Schneider, J.E., Bhattacharya, S., Hardy, A., Nolan, P.M., Tripodis, N., Depew, M.J., Chandrasekara, R., Duncan, G., Sharpe, P.T., Greenfield, A., Denny, P., Brown, S.D.M., Ragoussis, J., Arkell, R. Dissecting the genetic complexity of human 6p deletion syndromes using a region-specific, phenotype-driven mouse screen.  (2005)  Proc Natl Acad Sci U S A 102(35):12477-12482.
  • Blewitt, M.E., Vickaryous, N.K., Hemley, S.J., Ashe, A., Bruxner, T.J., Preis, J.I., Arkell, R., Whitelaw, E.  An ENU screen for genes involved in variegation in the mouse.  (2005)  Proc Natl Acad Sci U S A 102(21):7629-34.
  • Brown, L., Paraso, M., Arkell, R., Brown, S.  In vitro analysis of partial loss-of-function ZIC2 mutations in holoprosencephaly: alanine tract expansion modulates DNA binding and transactivation.  (2005)  Hum. Mol. Genet. 14(3):411-20.
  • Bogani, D., Warr, N., Elms, P., Davies, J., Tymowska-Lalanne, Z., Goldsworthy, M., Cox, R.D., Keays, D.A., Flint, J., Wilson, V., Nolan, P., Arkell, R. New semidominant mutations that affect mouse development.  (2004)  Genesis 40(2):109-117.
  • Mallon, A-M., Wilming, L., Weekes, J., Gilbert, J.G.R., Ashurst, J., Peyrefitte, L., Matthews, L., Cadman, M., McKeone, R., Sellick, C., Arkell, R., Botcherby, M.R.M., Strivens, M.A., Campbell, R.D., Gregory, S., Denny, P., Hancock, J.M., Rogers, J., Brown, S.D.M.  Organization and evolution of a gene-rich region of the mouse genome: a 12.7 Mb region deleted in the Del(13)Svea36H mouse.  (2004)  Genome Research 14(10):1888-1901.
  • Elms, P., Scurry, A., Davies, J., Willoughby, C., Hacker, T., Bogani, D., Arkell, R.  Overlapping and distinct expression domains of Zic2 and Zic3 during mouse gastrulation.  (2004)  Gene Expr. Patterns 4(5):505-511.
  • Elms, P., Siggers, P., Napper, D., Greenfield, A., Arkell, R.  Zic2 is required for neural crest formation and hindbrain patterning during mouse development.  (2003)  Dev. Biol. 264:391-406.
  • Curtin, J.A., Quint, E., Tsipouri, V., Arkell, R.M., Cattanach, B., Copp, A.J., Henderson, D.J., Spurr, N., Stanier, P., Fisher, E.M., Nolan, P.M., Steel, K.P., Brown, S.D., Gray, I.C., Murdoch, J.N.  Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse.  (2003)  Curr. Biol. 13(13):1129-1133.
  • Murdoch, J.N., Henderson, D.J., Doudney, K., Gaston-Massuet, C., Phillips, H.M., Paternotte, C., Arkell, R., Stanier, P., Copp, A.J.  Disruption of scribble (Scrb1) causes severe neural tube defects in the circletail mouse.  (2003)  Hum. Mol. Genet. 12(2):87-98.
  • Arkell, R.M., Cadman, M., Marsland, T., Southwell, A., Thaung, C., Davies, J.R., Clay, T., Beechey, C., Evans, E.P., Strivens, M.A., Brown, S.D.M., Denny, P.  Genetic, physical and phenotypic characterisation of the Del(13)Svea36H mouse mutant.  (2001)  Mammalian Genome 12:687-694.
  • Episkopou, V., Swan, D., Timmons, P., Walsh, J., Andrew, R., Arkell, R.  Induction of the mammalian node requires Arkadia function in the extraembryonic lineages.  (2001)  Nature 410:825-30.
  • Nolan, P.M., Peters, J., Strivens, M., Rogers, D., Hagan, J., Spurr, N., Gray, I.C., Vizor, L., Brooker, D., Whitehill, E., Washbourne, R., Hough, T., Greenaway, S., Hewitt, M., Liu, X., McCormack, S., Pickford, K., Selley, R., Wells, C., Tymowska-Lalanne, Z., Roby, P., Glenister, P., Thornton, C., Thaung, C., Stevenson, J-A., Arkell, R., Mburu, P., Hardisty, R., Kiernan, A., Erven, A., Steel, K.P., Voegeling, S., Guenet, J-L., Nickols, C., Sadri, R., Naase, M., Isaacs, A., Davies, K., Browne, M., Fisher, E.M.C., Martin, J., Rastan, S., Brown, S.D.M., Hunter, J.  A systematic genome-wide phenotype-driven mutagenesis programme for gene function studies in the mouse.  (2000)  Nature Genetics 25(4):440-443.
  • Sheardown, S.A., Duthie, S.M., Johnston, C.M., Newall A.E., Formstone, E.J., Arkell, R.M., Nesterova, T.B., Alghisi, G.C., Rastan, S., Brockdorff, N.  Stabilization of Xist RNA mediates initiation of X chromosome inactivation.  (1997)  Cell 91(1):99-107.
  • Arkell, R., Beddington, R.S.P.  BMP-7 influences pattern and growth of the developing hindbrain of mouse embryos.  (1997)  Development 124:1-12.
  • Harrison, S.M., Dunwoodie, S.L., Arkell, R.M., Lehrach, H.,  Beddington, R.S.P.  Isolation of novel tissue-specific genes from cDNA libraries representing the individual tissue constituents of the gastrulating mouse embryo.  (1995)  Development 121:2479-2489.

All publications

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