Grant: Operating Grant

Limbs in all animals, from fruit flies to humans, begin as small clusters of embryonic cells. The cells in these clusters divide and become distinct from each other (a process called differentiation) during development resulting in an enormous increase in cell number, and size. My lab wants to understand limb development. Ultimately, we would like to know every step that shapes a clusters of cells in the embryo to the fully-formed of adult limb. We employ the fruit fly, Drosophila melanogaster, as a model organism. The fly has the advantage of great genetic methods that allow for to find important genes and to turned them on and off in development. One of the key events that happens in cells is that they express special genes called "selector genes". Selector genes encode proteins that turn other genes on or off and are the key to deciding what sort of structure a cell will "choose" to make. We are studying a selector gene called midline, which controls the development of the entire ventral surface of the fly leg. When midline is not functioning all ventral structures develop as dorsal instead (if you imagine that the palm of your hand developed instead as a second version of the back of your hand then you would have a pretty good idea about the effect of midline mutants). The opposite happens too: when we turn on midline in dorsal cells, they turn into ventral (now imagine the back of your hand instead looking like a second palm!). We are trying to understand how midline is able to do this to cells. We think that midline can turn one set of genes on - the genes that make cells be 'ventral' and turn other genes off - the genes that make cells be 'dorsal'. What is most amazing, is that same sorts of genes also act in human development and cause all sorts of human congenital anomalies (birth defects) and so by understanding midline we will not only learn something new and fundamental about biology, but it may also help us to understand why congenital anomalies happen.