Grant: CIHR Fellowship

The human face and limb are supported by an intricate arrangement of bones, nerves and muscles. The same tissues are used in all parts of these regions but they are arranged in particular patterns so that a clear distinction is made between the outgrowing structures (like the upper jaw vs the lower jaw, anterior vs posterior fingers). This identity of the jaws and limb are established much earlier, during embryonic development. Our work focuses on the early embryonic stages when tiny buds of tissue surrounding the mouth and limb buds are just forming. We are using the chicken embryo as our model organism because it is possible to alter jaw identity and limb patterning in a reproducible way. This proposal uses embryo manipulations and other molecular technologies to identify the importance of the gene Peptidase Inhibitor 15 (PI15) in patterning the jaws and limbs. This gene codes for an interesting protein that inhibits the activity of other proteins. We have already determined that the PI15 gene is sufficient to make extra digits in the limb and clefts in the face. In this project we seek to identify the enzymes present in the embryo whose activity is inhibited by PI15. We are also going to decrease the amount of Pi15 in the face and limb to see the effects on jaw and digit patterning. This will show the role for PI15 during normal development. Our findings on the mechanisms of action of PI15 will be relevant to embryo development in general.