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PhD projects

Role of the Barx1 transcription factor in tooth and salivary gland development

1st Supervisor: Dr Isabelle Miletich

2nd Supervisor: Professor Paul Sharpe

Description of project

The homeobox transcription factor Barx1 has essential roles in the development of organs involved in food processing and digestion. These include teeth, salivary glands, the secondary palate, the stomach, intestine and oesophagus. This suggests an evolutionary link between Barx1 and feeding. However our analysis to date indicates that the molecular role of Barx1 in the development of these different but functionally connected organs is different. Thus the general question we wish to address is whether there is a common feature of Barx1 function that rendered it essential for the development of the feeding/digestive system. The aim of this project is to analyse gene expression changes recently identified from microarray analysis of wild-type and mutant developing salivary glands and teeth. This will involve a detailed bioinformatics analysis of the raw array data followed by gene expression verification using RT-PCR and in situ hybridisation and finally gene mutation and transgenic rescue experiments with downstream genes.

Duration of project: 4 years

Contact for further information

Professor Paul Sharpe

Email: paul.sharpe@kcl.ac.uk

Research Topic: Craniofacial Development and Stem Cell Biology

References relating to the project

Woo, J, Miletich I, Kim B-M, Sharpe PT, Shivdasani RA. (In press) PLOS One. Barx1-mediated inhibition of Wnt signaling in the mouse thoracic foregut controls tracheo-esophageal septation and epithelial differentiation.

Kim B-M, Buchner G, Miletich I, Sharpe PT and Shivdasani RA (2005) Developmental Cell 8, 611-622. The stomach mesenchymal transcription factor Barx1 specifies gastric epithelial identity through inhibition of transient Wnt signalling.

Miletich I, Buchner G and Sharpe PT (2005) J. Anat. 207, 619-622. Barx1 and evolution of feeding.

Tucker A.S., Matthews K and Sharpe P.T. (1998) Science 282, 1136-1138. Transformation of tooth type by inhibition of BMP signalling.

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