Development of the vertebrate limb is a complex example of pattern formation requiring cellular proliferation, differentiation, apoptosis and tissue rearrangement. The extensive tissue remodeling required to produce functional digits utilizes a multitude of enzymes and growth factors to eliminate both cells and extracellular matrix (ECM). Specifically, we are interested in understanding how the ECM is degraded during digitation of the developing limb. Matrix metalloproteinases (MMPs) are a family of structurally related, zinc-containing enzymes that degrade various components of the extracellular matrix. Recent studies indicated that MMP-2 plays a pro-apoptotic role in several systems. We are interested in the potential role MMP-2 might play during limb formation in the chick. We hypothesize that matrix breakdown precedes and may, in fact, initiate programmed cell death during digitation. In order to test this hypothesis, we are examining the effects of knocking down the expression of MMP-2 enzyme activity by using inhibitory Morpholino antisense oligos.
President of the Kansas Academy of Science, 2012