Topic: Mysterious phenotypes
Hiromi Y, Mlodzik M, West SR Rubin GM, Goodman CS
Ectopic expression of seven-up produces cell fate changes during ommatidial assembly.
Development 118: 1123-1135, 1993

The topic of this week refers to unexpected phenotypes that can arise from misexpression of genes. Artificial misexpression is a commonly used strategy to probe gene function. By testing what a gene "can" do in a abnormal spacial or temporal environment, one can gain information about the mode of gene activity that cannot be obtained by simply observing the loss of gene function. However such operations sometimes produces unexpected phenotypes that appear inconsistent with the proposed normal function of the gene. Since every unexpected result is a potential entry point to a new discovery, such findings should be cherished, however bizarre it may seem in the beginning.

This week we will take up one such case from my own experience. The paper deals with a gene called seven-up (svp), which encodes a transcription factor belonging to nuclear receptors. Based on the loss of function phenotype, the function of the svp gene appeared to be a genetic switch between two cell identities, i.e. the cells choose between two neuronal types depending on whether or not the svp gene is expressed. Thus misexpression of the svp gene was expected to confer the cell identity corresponding to the svp-ON state. However that was not (the only) phenotype obtained; svp misexpression produced many other kinds of cell fate transformations in various cell types. I was unable to bring this finding to a new discovery, either on the mode of svp gene function or on cell fate determination in general.

We would like to discuss what are potential reasons for these mysterious phenotypes, and what could be done to test such hypotheses.