The Developmental Genetics Laboratory studies the molecular mechanisms that pattern developing animals such that each cell adopts a fate appropriate to its position in the embryo and coordinated with its neighbours. We have focussed mainly on segmentation, the generation of repeated (metameric) groups of cells that underlies the body plan of most higher eukaryotic organisms, with particular interests in the molecular processes that underlies spatial and temporal asymmetries.

In Drosophila, early embryonic pattern is established within a single cell. Localised maternal RNAs direct the molecular asymmetries that establish the anteroposterior and dorsoventral axes of the future embryo. These spatial cues activate a cascade of segmentation genes in the early fertilised egg, leading to striped expression of genes that subdivide the embryo into repeated segments. Many segmentation genes encode transcriptional regulators that diffuse and form morphogenetic gradients within the embryo, thereby triggering expression of different target genes in different regions of the embryo.

By contrast, vertebrate segmentation takes place in a multicellular environment and is linked to growth. Segments arise sequentially, under the influence of the "segmentation clock", a molecular oscillator that drives cyclic transcription and tells cells when to form a new segmental boundary. However, the molecular basis of the clock is uncertain.

Current Research
Our studies on Drosophila concentrate on two aspects of early pattering: the establishment of intracellular asymmetry via RNA localisation within the blastoderm embryo, and mechanisms of transcriptional repression. We study transport of RNAs and organelles by molecular motors(reviewed in Kloc et al., 2002). using a combination of genetic, biochemical and cell biology techniques, with particular interests in how cargoes are recognised and how they, and other pathways influence motor activity. In addition, our genetic analysis of the Hairy family of repressors during early Drosophila development has led to structural studies of repressor/corepressor action and interests in repressor action in both Drosophila and vertebrates.

In studying vertebrate segmentation, we use a variety of model embryo systems including chicken, mouse and zebrafish to establish the molecular nature and circuitry of the clock that generates oscillatory transcription and segmentation (reviewed in Bessho & Kageyama, 2003). We are also embarking on a study of axial growth of the embryo, in particular of the axial stem cells that drive lengthening of the posterior body axis.