Molecular Embryology Team
Team Leader: Professor Peter Rigby
Location: Chester Beatty Laboratories, London
Section: Section of Gene Function and Regulation
An increasing number of human pathological conditions, including cancer, can be ascribed either directly to a malfunctioning gene or to a genetically associated predisposition. In the most obvious cases the underlying cause of the pathology is a faulty gene product. However a gene comprises more than just the instructions for making its protein, it also contains the control mechanism, the on-off switch, that ensures that the gene’s product is made in the correct place, at the correct time and in the correct developmental sequence. We are interested primarily in these control mechanisms and we are studying them in the context of how cell fate and identity decisions are made during embryonic development, and in particular in the biochemical pathways that link extra-cellular inductive signals to the transcriptional machinery in the nucleus.
We have focused our attention on the process of somitogenesis for several reasons. Firstly, each pair of somites has a distinct segmental identity, most obviously revealed by the morphology of the vertebra derived from it. Somitogenesis thus provides an excellent system in which to try to understand how positional identity along the body axis is specified. Secondly, as each somite compartmentalises to give rise to the three lineages which are the precursors to bone bone and cartilage, skeletal muscle and skin, well-defined decisions are made about cell fate. This provides a fine model in which to study the mechanisms by which pluripotent progenitor cells are directed towards a particular differentiation pathway. Thirdly, the anatomy of the mid-gestation mouse embryo means that it is relatively easy to define, with considerable precision, patterns of gene expression. One can thus compare the expression of the endogenous gene, as revealed by in situ hybridisation, with the expression of wild type or mutant transgenes, as revealed by histochemical staining to detect the product of an appropriate reporter gene.
Our general approach has been to take genes that are intrinsically of wide general interest such as the homeobox genes and the genes controlling muscle differentiation, then to try to understand how their transcription is controlled using the power of transgenic mouse technology. In each case our ultimate objective is to identify (or know the name) of each of the transcription factors that control the chosen regulatory gene so that we can then study how the activities of these factors are modulated, and thus build up a picture of the signal transduction pathways, and signals, involved in the developmental decision.
In the Section of Gene Function and Regulation
