Professor Philip W. Ingham: Research
Our research group uses two model organisms – the fruit fly Drosophila and the tropical zebrafish, Danio rerio – to analyse the genetic control of embryonic development. My early work on the establishment of segmentation in the Drosophila embryo (for a review, see Ingham, 1988) has led to our long standing interest in the Hedgehog signalling pathway (for review, see Ingham & McMahon, 2001).
Much of our current research centres around the mechanisms and functions of Hedgehog signalling. Using the sophisticated genetics and in vivo imaging techniques available in Drosophila we are investigating the mechanisms of action of the Hh receptor protein, Patched and of Smoothened, the serpentine protein essential for transduction of the Hh signal (see for example, Strutt et al 2001).
In vertebrate embryos. the notochord is a major source of Hh signals. Our studies in the zebrafish are focussed primarily on the role of notochord derived Hh signalling in specifying distinct muscle lineages and cell types.
In addition, we are using genetic analysis and gene expression profiling to identify genes required for the differentiation of muscles in response to Hh signals (for example, see Roy et al 2001).
Other projects currently ongoing in the lab include the analysis of Tbx gene function in cardiac development and the role of retinoic acid and Hh signalling in the specification and differentiation of endodermal organs.
References
- Ingham, P.W. (1988). The molecular genetics of embryonic pattern formation in Drosophila. Nature. 335:25-34.
- Ingham PW, McMahon AP. (2001) Hedgehog signaling in animal development: paradigms and principles. Genes & Devl. 15: 3059-87.
- Roy, S., Wolff, C and Ingham, P.W. (2001). The u-boot mutation identifies a Hedgehog regulated myogenic switch for fibre-type diversification in the zebrafish embryo. Genes & Devl. 15: 1563-1576.
- Strutt, H. Thomas, C. Nakano, Y. Stark, D. Neave, B. Taylor, AM and Ingham, PW (2001) Mutations in the Sterol Sensing Domain of Patched suggest a Role for Vesicular Trafficking in Smoothened Regulation. Current Biology. 11: 608-613