Research overview
This page presents a simplified explanation of our research meant in particular for the undergraduate or beginning graduate student interested in pursuing research in our lab. Contact Dr. Dobens for further information.
The first section provides the background to the problem of tissue patterning, followed by a section devoted to the model system that is the focus of our studies, concluding with a section describing our findings for the role of the bunched gene in cell migration in this tissue.
Problem of tissue patterning
Tissues and organs in all animals are formed from the ordered proliferation, migration and differentiation of cells. Cells form epithelial sheets which change shape and rearrange to build complex biological structures. Cell-cell communication forms the basis by which cell groups organize their behaviors, however the molecular mechanisms underlying the ability of cells to coordinate these complex activities remains poorly understood.
Drosophila oogenesis as a developmental model system
The fly ovary offers a simple and accessible model tissue to understand how an unpatterned epithelial sheet of cells generates clearly distinct cell types which migrate and produce specific features of the mature eggshell. Almost every major, conserved cell signaling pathway is required for its formation, including the Hedgehog/Sonic hedgehog, Wingless/Wnt and Dpp/BMP pathways. Using a wealth of molecular markers and genetic tools, we can manipulate gene levels and examine the effects on cell differentiation. In this way we can sort out how signaling pathways interact during organogenesis.
The role of the bunched gene in tissue patterning
Our studies of the Drosophila bunched gene provide a good example of how the ovary can be used to study the role of tissue-specific gene expression in patterning. bunched encodes a DNA-binding transcription factor that is a member of the TSC-22/GILZ family of genes that repress gene expression. In humans these genes exhibit tumor suppressor properties.
bunched has developmental functions during formation of a wide variety of organs in the fly but in the ovary its role is best understood. By raising and lowering levels of EGF and BMP morphogens in this tissue, we have show that bunched is activated and repressed, respectively, by these signals. Complimentarily, we have shown that bunched is required to repress Notch signaling to set a domain of reduced cell mixing - a boundary - between two cell groups.
Thus bunched appears to play a central role in tissue patterning: regulated by long-range signals like EGF and BMP, bunched regulates in turn short-range Notch signaling to define cell fates in a morphogen gradient. Our ongoing screens for genes that interact with bunched will map out the conserved signaling pathways that interact with bunched in the ovary and in other fly tissues. As well, we are interested in two isoforms of bunched generated by alternative splicing that indicate bunched has cellular functions we do not yet understand.
