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Current position
Senior Fellow
Research interests
Research within this
programme is focused on the identification and characterisation
of genes that are required for mammalian embryonic development.
Adult form and function is dependent upon the events of embryogenesis
and it is crucial for human health that we gain a better understanding
of the genetic control of development. There are now over 3000
documented non-chromosomal, multiple congenital anomaly syndromes.
Moreover, in recent years it has been recognised that the study
of embryology not only enhances our knowledge of congenital defects
but also the understanding of later onset diseases that involve,
for example, the inappropriate reactivation of genes that control
cell growth and differentiation.
One of the most crucial
stages of embryonic development is gastrulation. During this period
cell movement and cell-cell communication directs differentiation
such that a highly patterned embryo with three recognisable axes
(anterior-posterior, dorsal-ventral and left-right) is formed.
In the mouse, gastrulation begins just after implantation at around
6.5 days post coitum (dpc) and by 9.5 dpc the embryo contains
the rudiments of almost every adult structure. In order to identify
genes that function during gastrulation we use genetic screens
to recover mutants that have a visible mid-gestation phenotype.
We are currently investigating several mutant strains that exhibit
defective forebrain development. We have identified the mutated
gene in many of these strains and are characterising the morphological
and molecular defects to reveal the function of the mutated gene.
Selected Publications
Garrick, D., Sharpe,
J.A., Arkell, R., Smith, A.J., Wood, W.G., Higgs, D.R., Gibbons,
R.J. (2006) Loss of Atrx affects trophoblast development and the
pattern of X-inactivation in extraembryonic tissues. PLOS Genetics
2:e58 438-450.
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. and Arkell, R.M. (2005)
Dissecting the genetic complexity of human 6p deletion syndromes
by using a region-specific, phenotype-driven mouse screen. Proc.
Natl. Acad. Sci. (USA) 102: 12477-12482
Blewitt, M.E., Vickaryous, N.K., Hemley, S.J., Ashe, A., Bruxner,
T.J., Preis, J.I., Arkell, R., and Whitelaw, E. (2005) An N-ethyl-N-nitrosourea
screen for genes involved in variegation in the mouse. Proc. Natl.
Acad. Sci. (USA) 102: 7629-7634
Brown, L., Paraso, M., Arkell, R. and Brown, S. (2005) In vitro
analysis of partial loss-of-function ZIC2 mutations in holoprosencephaly:
alanine tract expansion modulates DNA binding and transactivation.
Hum. Mol. Genet. 14:411-420
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. and Arkell, R. New semidominant mutations that affect
mouse development. (2004) Genesis 40 (2):109-117.
Elms, P., Scurry, A., Davies, J., Willoughby, C., Hacker, T.,
Bogani, D. and 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. and Arkell,
R. Zic2 is required for neural crest formation and hind-brain
patterning during mouse development. (2003) Dev. Biol., 264
: 391-406
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