The role of the Drosophila eyeless gene during eye and brain development: From structure-function analysis to target genes.

摘要

The Drosophila Pax6 homolog Eyeless is a conserved transcription factor that has been shown to be required for eye, and more recently, brain development. The Eyeless protein consists of two DNA binding domains, the N-terminal paired domain and the homeodomain, which are separated by a linker region of unknown function, and a C-terminal domain rich in proline, serine, and threonine. Mutations within the eyeless gene result in a decrease in eye size to total loss of the eye, head patterning defects, and defects in major brain neuropils, such as the optic lobes, mushroom bodies, and central complex. However, the requirement for the major domains of the Eyeless protein has not been studied. To address this, I characterized and studied newly described eyeless alleles encoding either a truncated Eyeless protein or a single amino-acid substitution within one of the protein domains to determine the requirement of each of the four Eyeless domains in eye and brain development. Furthermore, I describe for the first time complete rescue of the eyeless eye and brain phenotypes, demonstrating that an intact Eyeless protein is required for normal development of these structures. I also describe a role for eyeless in the differentiation and function of the insulin-producing cells in the pars intercerebralis of the Drosophila brain. In addition, I describe that within these neurosecretory cells, Eyeless regulates the transcription of two cell adhesion molecules, neuroglian and fascielin II, which I show are also required for proper differentiation of these cells. Finally, I describe a screen for transcriptional targets of Eyeless using enhancer traps known to have preferential mushroom body expression. By overexpressing Eyeless in these lines, we were able to identify five genes as Eyeless transcriptional targets.