Abstract

The elbow/no 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.

Highlights

  • The developing retina of Drosophila melanogaster is a powerful model for studying the specification of cell fates within a retinal mosaic

  • 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

  • Human homologs of Elbow and No ocelli have been identified as promoters of luminal breast cancer

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Summary

Introduction

The developing retina of Drosophila melanogaster is a powerful model for studying the specification of cell fates within a retinal mosaic. One important aspect is the localized specification of photoreceptor cell types in response to Wg/Wnt signaling. Wg emanating from the head cuticle specifies specialized ommatidia at the dorsal rim of the developing retina [1,2,3]. We show that the Drosophila NET family zinc finger proteins Elbow (Elb) and No ocelli (Noc) play a crucial role in this process. The patterning of the ommatidial mosaic in the dorsal periphery of the retina serves as an attractive model to characterize the different roles of NET proteins

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