Grant: Operating Grant

One of the most common birth defects in Canada is cleft lip with or without cleft palate. Clefts arise during the embryonic period and lead to significant social and physical burdens for affected individuals. There are thought to be multiple genes that together contribute to increased risk of clefting. In addition environment also plays a role. We are using the avian embryo because it is one of the few animals in which it is possible to directly work on the face while it is developing. Furthermore, it is possible to induce cleft lip reliably. Our goal in this grant is to increase or decrease the levels of growth factors specifically in the areas of the face that form the lip and study their effect on lip fusion. Using cells extracted from the face we will be exploring the effects of one type of signal, WNT proteins, on gene expression. DNA from these facial cells will be laid over highly sensitive microarrays containing all of the chicken genes. We will interrogate the arrays and through this analysis we will make surprising and significant discoveries about genes that contribute to clefting. In addition we are going to transfer human mutations in one of the WNT genes that cause a craniofacial syndrome into the chicken. The goal is to explain the effect of the mutations on the way the protein works within the face. We use novel techniques that we developed in our own lab to tag facial cells with fluorescent markers so that we can map their movements within the growing face. To visualize the results several cutting edge imaging techniques will be used including a unique 3D scanner developed specifically for embryos and a white light, laser confocal microscope. Using these tools we will understand much more precisely how changes in gene function can increase susceptibility to clefting. These results will lead to better understanding of the causes of clefting as well as other facial birth defects.