Research projects
The molecular basis of proximal-distal positional information in the vertebrate limb bud
Exactly how cells within the upper arm know to form one skeletal element, while cells in the hand form multiple is currently unknown. Accumulating evidence suggests that cells within the very early limb bud already know which skeletal element they will contribute to, however the molecular basis of this early fate specification is unclear.
To address this question, we plan to utilise the strength of the mouse system to genetically label precursor cells of the three limb segments (upper arm, mid arm and hand) with different fluorescent reporters. This will allow us access to these cells throughout development and to molecularly profile them as their identity is being specified.
High throughput screen for miRNAs relevant to limb and axial patterning
For the majority of miRNAs currently annotated, little or no functional information exists creating a major road-block in the field. Our recent success in developing an antagomiR-based knockdown strategy in chick now opens the way to perform a high throughput screen to identify additional developmentally relevant miRNAs.
We will generate an updated miRNA expression profile at key time points in development using microarray or deep sequencing based approaches. Functional analysis will include both retroviral based over-expression and antagomiR knockdown in chick. In mouse, we have pioneered an in utero ultrasound guided injection strategy to knockdown miRNA function in the developing embryo.
Full characterisation of miR-196 knockout phenotypes
The miR-196 family of miRNAs exhibits striking developmental expression and its members are predicted to control the expression levels of up to 10 different Hox genes. We have generated knockout mice for the miR-196 genes and a complete analysis of single, double and triple mouse mutant will be a significant focus of this lab.
The expected phenotypic analysis will involve both developmental studies as well as adult homeostasis and disease states.