Análisis funcional del gen nab en el desarrollo de drosophila melanogaster

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 15-12-2006Nab 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. In this project we analyze the role of Nab in Drosophila development. By employing genetic and molecular approaches we found that nab is required for proximodistal patterning of the wing imaginal discs and also for determining specific neuronal fates in the embryonic Central Nervous System. We identified two targets of Nab: the products of the zinc finger- encoding genes rotund and squeeze. Both gene products belong to the Kruppel family, as the vertebrate partners of Nab: the EGR transcription factors. 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 acts as a co- activator of Squeeze, so is required to limit the number of neurons that express the LIM-homeodomain gene apterous, and to specify the Tv neuronal fate through the activation of the FMRFa neuropeptide. Conversely, Nab act as a co-repressor of Rotund in wing development, and is required to limit the expression of the gene wingless/WNT in the wing hinge, where Wg plays a mitogenic role. We demonstrate the requirement of vg in the activation of nab in the wing disk, and the limitation of its expression by zfh2. We show by pull-down assays that Nab binds directly to Rotund and Squeeze via their conserved C-terminal domain. Going further in the molecular mechanism underling the repression of the targets of Rn by Nab, we show preliminary results that involve the general corepressor dCtBP as a possible partner of NabPeer reviewe

The role of tarsal-less in Drosophila wing imaginal disc development

Trabajo presentado en el 1st PhD and Postdoc Symposium (From Cells to Organs), celebrado en Barcelona el 16 y 17 de abril de 2012.N