Specification of pattern and cell fate in the developing eye, using Drosophila.
I am interested in the developmental biology of the nervous system. The workings of the complex nervous systems of higher animals (such as ourselves) is surely the greatest remaining mystery in biology. In such systems function is related to structure, and thus it is of interest how the many nerve cells achieve their correct cell-types and positions in space. In recent years the most rapid advances in developmental biology (and biology in general) have come from a reductionist and genetic approach. My lab approaches nervous system development by the use of a simple model system, with powerful genetic tools: the compound eye of Drosophila melanogaster. This fly's eye consists of a large number of simple unit eyes (or ommatidia), which are comprised of only twenty cells (eight photoreceptor neurons and twelve accessory cells). These cells, and the ommatidia themselves, must be of precise position and shape for the optical and neural functioning of the eye. The adult eye develops from an unpatterned monolayer epithelium in the larva (the eye field of the eye-antennal imaginal disc). Cell-type determination is associated with a progressive wave (the morphogenetic furrow) which sweeps across the eye field over a period of about two days. The morphogenetic furrow coordinates cell division cycles, gene expression, cell fate allocation and pattern formation. Thus the morphogenetic furrow is a complex and beautiful phenomenon, which touches on many of the more general problems in developmental biology. My research group is focused on uncovering the molecular mechanisms that run the furrow.
We and others have showed that the furrow is driven forward by the forward diffusion of the Hedgehog protein. In the furrow a number of proteins interact to control pattern and cell fate. Amongst these, we have been concentrating on the Drosophila homolog of the EGF-receptor, and some of its ligands. We have also studied the effects of another diffusible signal, the Wingless protein, on furrow regulation, and we have studied the mechanisms that determine tissue polarity in the developing eye. We have also found that a steroid hormone (ecdysone) acts in eye development. Thus our studies of eye development have been of significance, in that they touch on general issues, such as control of cell fate, or cancer (through our studies of the EGF-receptor pathway). The orthodox view of the evolution of eyes has been that they are polyphyletic. However, as with segmentation, recent genetic and molecular studies have shown that insect and vertebrate eyes are homologs. Thus the molecular biology of fly eye development may be directly relevant to the development of the vertebrate eye.
