title: Mutational analysis of the eyeless gene and phenotypic rescue reveal that an intact Eyeless protein is necessary for normal eye and brain development in Drosophila.
abstract: Pax6 genes encode evolutionarily highly conserved transcription factors that are required for eye and brain development. Despite the characterization of mutations in Pax6 homologs in a range of organisms, and despite functional studies, it remains unclear what the relative importance is of the various parts of the Pax6 protein. To address this, we have studied the Drosophila Pax6 homolog eyeless. Specifically, we have generated new eyeless alleles, each with single missense mutations in one of the four domains of the protein. We show that these alleles result in abnormal eye and brain development while maintaining the OK107 eyeless GAL4 activity from which they were derived. We performed in vivo functional rescue experiments by expressing in an eyeless-specific pattern Eyeless proteins in which either the paired domain, the homeodomain, or the C-terminal domain was deleted. Rescue of the eye and brain phenotypes was only observed when full-length Eyeless was expressed, while all deletion constructs failed to rescue. These data, along with the phenotypes observed in the four newly characterized eyeless alleles, demonstrate the requirement for an intact Eyeless protein for normal Drosophila eye and brain development. They also suggest that some endogenous functions may be obscured in ectopic expression experiments.
authors: Laboratory of Developmental Genetics, VIB, and Center of Human Genetics, Katholieke Universiteit Leuven, Herestraat 49, Box 602, B-3000, Leuven, Belgium.
authors: Jason
authors: J
authors: Clements
authors: Korneel
authors: K
authors: Hens
authors: Srinivas
authors: S
authors: Merugu
authors: Beatriz
authors: B
authors: Dichtl
authors: H Gert
authors: HG
authors: de Couet
authors: Patrick
authors: P
authors: Callaerts
mesh_terms: D000483:Alleles; D000818:Animals; D001921:Brain / Q000254:growth & development*; D002478:Cells, Cultured; D054910:Compound Eye, Arthropod / Q000254:growth & development*; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D005816:Genetic Complementation Test; D005838:Genotype; D006257:Head / Q000254:growth & development; D008297:Male; D020125:Mutation, Missense; D010641:Phenotype; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C113278:ey protein, Drosophila