Genetic Dissection of Photoreceptor Subtype Specification by the Drosophila melanogaster Zinc Finger Proteins Elbow and No ocelli

摘要

The elbowo ocelli ( elb / noc ) complex of Drosophila melanogaster encodes two paralogs of the evolutionarily conserved NET family of zinc finger proteins. These transcriptional repressors share a conserved domain structure, including a single atypical C2H2 zinc finger. In flies, Elb and Noc are important for the development of legs, eyes and tracheae. Vertebrate NET proteins play an important role in the developing nervous system, and mutations in the homolog ZNF703 human promote luminal breast cancer. However, their interaction with transcriptional regulators is incompletely understood. Here we show that loss of both Elb and Noc causes mis-specification of polarization-sensitive photoreceptors in the ‘dorsal rim area’ (DRA) of the fly retina. This phenotype is identical to the loss of the homeodomain transcription factor Homothorax (Hth)/dMeis. Development of DRA ommatidia and expression of Hth are induced by the Wingless/Wnt pathway. Our data suggest that Elb/Noc genetically interact with Hth, and we identify two conserved domains crucial for this function. Furthermore, we show that Elb/Noc specifically interact with the transcription factor Orthodenticle (Otd)/Otx, a crucial regulator of rhodopsin gene transcription. Interestingly, different Elb/Noc domains are required to antagonize Otd functions in transcriptional activation, versus transcriptional repression. We propose that similar interactions between vertebrate NET proteins and Meis and Otx factors might play a role in development and disease. Author Summary The eyes of many animals contain groups of photoreceptor cells with different chromatic sensitivities that can be arranged in complex patterns. It is of great interest to identify the genes and pathways shaping these ‘retinal mosaics’ which include stochastically distributed groups of cells, versus highly localized ones. In many insect eyes, which are composed of large numbers of unit eyes, or ommatidia, specialized photoreceptors are found only in the dorsal periphery, where they face the sky. These ommatidia are responsible for detecting linearly polarized skylight, which serves as an important navigational cue for these animals. Here we describe how two closely related proteins called Elbow and No ocelli interact with the transcription factors Homothorax and Orthodenticle to correctly specify the polarization detectors at the dorsal rim of the retina of Drosophila melanogaster . Interestingly, all four proteins are evolutionarily conserved from worms to humans, and they appear to be involved in similar developmental processes across species. Furthermore, human homologs of Elbow and No ocelli have been identified as promoters of luminal breast cancer. The newly identified role of these two proteins within a regulatory network might therefore enable new approaches in a number of important processes.