The Drosophila compound eye has provided a genetic approach tounderstanding the specification of cell fates during differentiation. The eye ismade up of some 750 repeated units or ommatidia, arranged in a lattice. Thecellular composition of each ommatidium is identical. The arrangement of thelattice and the specification of cell fates in each ommatidium are thought to occurin development through cellular interactions with the local environment. Manymutations have been studied that disrupt the proper patterning and cell fating in theeye. The eyes absent (eya) mutation, the subject of this thesis, was chosen becauseof its eyeless phenotype. In eya mutants, eye progenitor cells undergoprogrammed cell death before the onset of patterning has occurred. The moleculargenetic analysis of the gene is presented.
The eye arises from the larval eye-antennal imaginal disc. During the thirdlarval instar, a wave of differentiation progresses across the disc, marked by afurrow. Anterior to the furrow, proliferating cells are found in apparent disarray.Posterior to the furrow, clusters of differentiating cells can be discerned, thatcorrespond to the ommatidia of the adult eye. Analysis of an allelic series of eyamutants in comparison to wild type revealed the presence of a selection point: awave of programmed cell death that normally precedes the furrow. In eyamutants, an excessive number of eye progenitor cells die at this selection point,suggesting the eya gene influences the distribution of cells between fates of deathand differentiation.
In addition to its role in the eye, the eya gene has an embryonic function.The eye function is autonomous to the eye progenitor cells. Molecular maps of theeye and embryonic phenotypes are different. Therefore, the function of eya in theeye can be treated independently of the embryonic function. Cloning of the gene reveals two cDNA's that are identical except for the use of an alternatively-spliced5' exon. The predicted protein products differ only at the N-termini. Sequenceanalysis shows these two proteins to be the first of their kind to be isolated.Trangenic studies using the two cDNA's show that either gene product is able torescue the eye phenotype of eya mutants.
The eya gene exhibits interallelic complementation. This interaction is anexample of an "allelic position effect": an interaction that depends on the relativeposition in the genome of the two alleles, which is thought to be mediated bychromosomal pairing. The interaction at eya is essentially identical to aphenomenon known as transvection, which is an allelic position effect that issensitive to certain kinds of chromosomal rearrangements. A current model forthe mechanism of transvection is the trans action of gene regulatory regions. Theeya locus is particularly well suited for the study of transvection because themutant phenotypes can be quantified by scoring the size of the eye.
The molecular genetic analysis of eya provides a system for uncoveringmechanisms underlying differentiation, developmentally regulated programmedcell death, and gene regulation.
