Previous and current research
We are interested in the molecular mechanisms that establish and maintain spatial patterning in early embryos. In Drosophila, we are focusing on intracellular asymmetries, and how mRNA transcripts are transported and localised in the unicellular embryo. In vertebrates, we are interested in the molecular oscillator (segmentation clock) that drives repeated production of segments, and in how this is related to axial growth of the embryo.

In Drosophila embryos, we have shown that intracellular localisation of mRNA transcripts helps target proteins to provide spatial cues that direct patterning. We have used rapid injection assays to identify components of the dynein motor complex that transports RNAs to the minus-ends of microtubules, and to analyse the RNA signals recognised by the complex. We have also visualised the localisation of injected wild-type and mutant transcripts in real time; our results indicate that recognition of the RNA cargo is directly linked to regulation of motor efficiency. We are currently using genetic and biochemical approaches to understand the specificity and control of RNA transport.

The vertebrate segmentation clock drives cyclic transcription of various target genes prior to formation of segment-boundaries. We have identified a regulatory region in the promoter of the lunatic fringe cycling gene that drives cyclic transcription in mouse embryos, and shown that is directly activated by Notch signalling. We are testing if oscillatory Notch signalling is a direct component of the segmentation clock, and investigating the circuitry that drives cyclic gene expression.

We have also started to study axial growth and patterning of vertebrate embryos which arises from a posterior "growth zone" which is believed to include self-renewing axial stem cells. We using transcriptional profiling of single cells to identify cell-type-specific markers in order to analyse the mechanisms controlling specification, maintenance and developmental potential of the stem cells and their progeny.

For more details on ongoing projects in the Developmental Genetics group, please visit the group's website.