4 YEAR PhD IN NEUROSCIENCE
Institute of Child Health
Developmental biology of neural tube defects
In the Neural Development Unit we are investigating the genetic, molecular and cellular basis of central nervous system development with particular reference to clinically important congenital malformations. Our previous work has succeeded in defining several steps in the embryonic pathway of neurulation, and has permitted a neural tube defect, spina bifida, to be prevented by a new method complementary to folic acid. Close links with Great Ormond Street Hospital for Children allow research findings to be applied to the clinical situation.
Embryonic mechanisms underlying neural tube defects in mouse genetic models
The purpose is to identify the molecular mechanisms that become disrupted in the Zic2 mutant mouse which develops severe spina bifida as a result of defective neural plate bending during neurulation. Techniques will include immunohistochemistry and in situ hybridisation on whole and sectioned mouse embryos. The lab makes extensive use of whole mouse embryo culture, a technique by which mouse embryos can be cultured intact during neurulation and subjected to a variety of experimental techniques (e.g. gene electroporation). A placement in the lab will provide an opportunity to gain experience of this powerful technique for analysing the developmental events during mammalian embryogenesis. MORE
Cogram, P., Hynes, A., Dunlevy, L. P. E., Greene, N. D. E., and Copp, A. J. (2004)
Specific isoforms of protein kinase C are essential for prevention of folate-resistant neural tube defects by inositol.
Hum. Mol. Genet. 13, 7-14
Copp, A. J., Greene, N. D. E., and Murdoch, J. N. (2003)
The genetic basis of mammalian neurulation.
Nat. Rev. Genet. 4, 784-793
Ybot-Gonzalez, P., Cogram, P., Gerrelli, D., and Copp, A. J. (2002)
Sonic hedgehog and the molecular regulation of neural tube closure
Development 129, 2507-2517