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Signalling and morphogenesis

The precise coordination of the many forces and growth factors acting upon embryonic tissues is required for the development of complex organs. We are interested in how intracellular signalling pathways are regulated during organogenesis. Many cell surface receptors use reversible tyrosine phosphorylation as a means of signal transduction. Studies in a number of biological systems have suggested that these signalling pathways are not merely ON/OFF switches but that subtle differences in signal strength and duration often result in profoundly different outcomes.

The broad aim of our research is to understand how intracellular signaling regulators of the Sprouty family are employed to coordinate morphogenesis of the cerebellum and pharyngeal pouches.

Cerebellar morphogenesis: The cerebellum is the brain’s control centre for motor coordination and defects in cerebellar development are often associated with ataxia or medulloblastoma, the most common type of childhood cancer. We are interested in how the cerebellum is constructed during embryonic and early postnatal development. Studies on conditional mid-hindbrain-specific Sprouty mutants have shown that these genes play important roles during postnatal cerebellar morphogenesis and we are investigating this process using inducible, conditional gene inactivation approaches in vivo.

Supported by the Wellcome Trust

Thymus organogenesis, pharyngeal pouch patterning and DiGeorge syndrome: Our recent experiments have indicated that several essential organs such as the thymus, parathyroid, middle ear and cranial sensory ganglia that develop wholly or in part from the pharyngeal apparatus exhibit multiple defects in Sprouty mutant mice. These same organs are affected in 22q11 deletion or DiGeorge syndrome and we are investigating the molecular and developmental basis of these defects in mouse embryos.

Supported by the Medical Research Council

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