Function of Drosophila Tbx1 (Org-1)

• Applicant: Professor Dr. Gert O. Pflugfelder
• Subject Area: General Genetics and Functional Genome Biology
• Term: from 2010 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 190273201

Drosophila Org-1 (Optomotor-blind related gene-1) is the only fly homolog in the Tbx1 subfamily of Tbox transcription factors. Mutations in several human TBX genes cause defects in limb and heart development. Overexpression of TBX2 and TBX3 is found in many forms of cancer. Mutations in TBX1 cause craniofacial dysplasia and a number of developmentally related defects (DiGeorge syn-drome) and may be a risk factor for schizophrenia. Org-1 is the least characterized of the eight Dro-sophila Tbx genes. Since Tbx proteins bind to highly related DNA target elements and tend to interact, cross-regulate and compete, a better knowledge of Org-1 function will contribute to the understanding of all Tbx proteins. Org-1 is an essential gene. Northern and in situ analysis suggest a predominantly embryonic function. RNAi knock-down also revealed a role in imaginal development. We plan to identify the role of org-1 in embryonic and later development. Org-1 target genes will be identified using a combination of bioinformatic, transcriptome, and proteome analytical tools. Functionally relevant domains in the Org-1 protein will be identified in cell culture and transgenic experiments. With this study, we want to learn some of the underpinnings of Tbx protein biological specificitiy.

• DFG Programme: Research Grants