BRIGHAM YOUNG UNIVERSITY
The purpose of this research is to identify the genetic basis underlying directional growth of cells in the embryonic limb (i.e., the limb mesenchyme). We have previously demonstrated that a structure found at the distal tip of the limb known as the apical ectodermal ridge (AER) is crucial for directional growth of the adjacent limb mesenchyme. We have also determined that signals from the AER activate a gradient of a second secreted molecule, Wnt5a. We have proposed that this gradient is important is helping limb mesenchyme cells to interpret directionality (i.e., increasing Wnt5a concentration determines the direction of growth). To test this hypothesis, we are examining whether introducing a secondary source of Wnt5a can redirect growth in limb mesenchyme cells both in vivo and in vitro. We are also testing whether blocking the ability of the limb mesenchyme to respond to Wnt5a inhibits the ability of the limb mesenchyme to grow directionally. The results of these experiments will be important as it is not clear how directed growth influences morphogenesis of organs. The results that we obtain here might have important implications for other tissues as there is strong evidence that the embryo employs the same signaling pathways in the 3-dimensional growth of several additional organs. There is also much evidence to suggest that cells losing their sense of directionality (polarity) underlies tumor formation. Hence these studies have important implications for human health.