Nab controls the activity of the zinc-finger transcription factors Squeeze and Rotund in Drosophila development

Nab proteins form an evolutionarily conserved family of transcriptional co-regulators implicated in multiple developmental events in various organisms. They lack DNA-binding domains and act by associating with other transcription factors, but their precise roles in development are not known. Here we analyze the role of nab in Drosophila development. By employing genetic approaches we found that nab is required for proximodistal patterning of the wing imaginal disc and also for determining specific neuronal fates in the embryonic CNS. We identified two partners of Nab: the zinc-finger transcription factors Rotund and Squeeze. Nab is co-expressed with squeeze in a subset of neurons in the embryonic ventral nerve cord and with rotund in a circular domain of the distal-most area of the wing disc. Our results indicate that Nab is a co-activator of Squeeze and is required to limit the number of neurons that express the LIM-homeodomain gene apterous and to specify Tv neuronal fate. Conversely, Nab is a co-repressor of Rotund in wing development and is required to limit the expression of wingless (wg) in the wing hinge, where wg plays a mitogenic role. We also showed by pull-down assays that Nab binds directly to Rotund and Squeeze via its conserved C-terminal domain. We propose two mechanisms by which the activation of wg expression by Rotund in the wing hinge is repressed in the distal wing.