Molecular analysis of cleft palate

Development of the lip and palate involves a complex series of highly integrated events that are frequently disrupted resulting in the congenital disoders cleft lip and cleft palate. Collectively, cleft lip and cleft palate have an estimated incidence of 1 in 500-2500 live births depending on geographic origin, racial and ethnic variation, and socio-economic status and result in considerable morbidity to affected families as individuals who exhibit this condition may experience problems with eating, speaking and hearing which can be corrected to varying degrees by surgery, dental treatment, speech therapy and psychosocial intervention. The frequent occurrence and significant burden imposed by cleft lip and cleft palate highlight the need to dissect the aetiology and molecular pathogenesis of this distressing condition.

Sonic hedgehog (Shh) has been shown to be a key regulator of palatal development. In this project, we will generate two high-throughput systems databases. First, we will determine Shh targets in the palatal mesenchyme by generating a highly filtered dataset. To enrich for direct Shh targets, we will compare palatal mesenchyme conditional Smoothened (Smo) loss- and gain-of-function microarrays and filter this dataset through a Gli Chromatin Immuno-Precipitation (ChIP) database. We will verify these targets in Smo mutant mice.

This project will therefore increase our understanding of the Shh signalling pathway during development of the secondary palate.