Sidekick, an adhesion molecule, controls the fates of the mystery cell in the Drosophila eye

Abstract

The Drosophila eye is composed of 800 ommatidia, each of I which contains 8 photoreceptor (R) cells. At the third larval instar stage, ommatidial clusters are assembled sequentially after the morphogenetic furrow (MF), an indentation that moves across the eye imaginal disc from the posterior to the anterior edge. One or two cells, which are originally included in the cluster, do not become neurons. They are referred to as mystery cells, as their fate is unknown. Previous studies have shown that sidekick (sdk), a member of the immunoglobulin superfamily, is required in the surrounding undifferentiated cells to prevent the mystery cells from inappropriately differentiating as R cells.;In this study, a Sdk antibody was generated and antibody staining revealed a low level of ubiquitous sdk expression after the MF. The expression is relatively higher in the mystery cells and the undifferentiated cells anterior to the ommatidial clusters, which correlates with the requirement of sdk function in the undifferentiated cells. The sdk rescue experiments showed that the expression of sdk in both the mystery cells and the abutting R cells is sufficient to rescue sdk.;Lateral sections showed that Sdk is apically localized. The intracellular domain of Sdk is responsible for its apical localization. However, the intracellular domain is dispensable for the rescue of sdk. It may enhance the function of endogenous sdk, which is expressed at a low level.;In vitro cell aggregation assay showed that sdk is able to mediate homotypic cell adhesion. A PDZ binding motif at the C-terminus of Sdk can facilitate cell aggregation.;Analysis of sdk ectopic expression phenotype showed that sdk is able to interfere with other signaling pathways that are involved in the determination of the ommatidial spacing ahead of the furrow and the maintenance of R cells during pupal stages. A specific dominant interaction was detected between ectopically expressed sdk and Star, a single transmembrane protein involved in processing an active ligand for the epidermal growth factor receptor (EGFR). Lack of a dominant genetic interaction of sdk with other components of the EGFR pathway suggests that sdk may interact with a novel signaling pathway mediated by Star.;Based on these results, a complex involving sdk via a homotypic or heterotypic interaction is proposed to regulate a novel signaling pathway that prevents the mystery cells from adopting a neuronal cell fate.