Nemo phosphorylates Eyes absent and enhances output from the Eya-Sine oculis transcriptional complex during Drosophila retinal determination

• DOI: 10.1016/j.ydbio.2012.02.030
• Publication Date: 2012-02-25T15:01:50Z
• Authors: Santiago A. Morillo; Lorena R. Braid; Esther M. Verheyen; Ilaria Rebay
• Keywords: NLK; Homeodomain Proteins; Transcriptional Activation; 0303 health sciences; Eye development; Organogenesis; Cell Biology; Eye; Retina; 03 medical and health sciences; Cell fate; Animals; Drosophila Proteins; Drosophila; Transcription factor; Mitogen-Activated Protein Kinases; Phosphorylation; Eye Proteins; Molecular Biology; Developmental Biology

The retinal determination gene network comprises a collection of transcription factors that respond to multiple signaling inputs to direct Drosophila eye development. Previous genetic studies have shown that nemo (nmo), a gene encoding a proline-directed serine/threonine kinase, can promote retinal specification through interactions with the retinal determination gene network, although the molecular point of cross-talk was not defined. Here, we report that the Nemo kinase positively and directly regulates Eyes absent (Eya). Genetic assays show that Nmo catalytic activity enhances Eya-mediated ectopic eye formation and potentiates induction of the Eya-Sine oculis (So) transcriptional targets dachshund and lozenge. Biochemical analyses demonstrate that Nmo forms a complex with and phosphorylates Eya at two consensus mitogen-activated protein kinase (MAPK) phosphorylation sites. These same sites appear crucial for Nmo-mediated activation of Eya function in vivo. Thus, we propose that Nmo phosphorylation of Eya potentiates its transactivation function to enhance transcription of Eya-So target genes during eye specification and development.