Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

The face is supported by an intricate arrangement of bones, cartilages and muscles. These structures are set up early in life, during the embryonic period before birth. At this time, all the cells look identical and yet genes are being turned on and off in a precise manner to distinguish the upper and lower jaw. Our work focuses on the early embryonic stages when tiny buds of tissue surrounding the mouth are just forming. We are using the chicken embryo as our model organism because the tissues are accessible during embryonic stages and it is possible to alter the patterns of bone and cartilage formation by changing gene expression. The proteins pursued in this application are called Wingless-related proteins or WNTs. We have already shown that one of the WNTs, WNT5A, is present within the cartilage-forming regions at early stages of development but then is excluded from mature cartilage. In cell cultures of lower jaw tissues, we showed that addition of WNT5A completely eliminates cartilage matrix, even though it is initially formed normally. This is a surprising result and one that we are gong to study further in this proposal. WNT5A activates a less commonly used WNT pathway, the non-canonical pathway, to affect cartilage. In this project, we seek to identify the genes present in the lower jaw whose activity leads to changes in cartilage matrix following WNT5A addition. We are also going to increase and decrease the amount of WNT5A in the embryonic chicken face to see the effects on growth and specification of bone and cartilage in the lower jaw. This will show the role for WNT5A during normal development. One day we hope to use this deep understanding of WNT5A to control skeletal formation in a controlled manner during healing after repair of congenital skeletal abnormalities, traumatic injuries or from bone diseases.