Elucidation of the role of Omb in omb-dependent enhancers

• Applicant: Professor Dr. Gert O. Pflugfelder
• Subject Area: Developmental Biology
• Term: from 2007 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 48083929

T-box (Tbx) proteins are a family of transcription factors found in all metazoans. They play important roles in development and function of animal organisms. Phylogenetically, they can be grouped into five subfamilies. Human genes of the Tbx2 subfamily (TBX2-TBX5) control the development of heart and appendages and currently are under investigation because of their role in tumor and stem cell biology. Optomotor-blind (Omb) is the only Drosophila member of the Tbx2 subfamily.The Tbx DNA binding domain is strongly conserved across all protein family members and all species. To current knowledge, all Tbx proteins can bind the same set of Tbx binding elements (TBEs). Currently, an insufficient number of TBEs, which mediate the action of individual Tbx proteins, is known to recognize individual sequence preferences.Omb controls many developmental processes in the fly: Brain (optic lobes), eye, limbs (particularly the wing), abdominal integument. In the wing disc, omb is expressed in the entire primordium of the wing blade (wing pouch) and in the dorsal and ventral hinge region. Omb expression is symmetrical with regard to the compartment boundaries which pattern the wing (dorso-ventral and anterior-posterior). Omb is essential for wing development and upon ectopic expression (in the notum region of the wing disc) is sufficient to induce development of a second wing pair. In spite of its symmetrical expression, Omb has different function in anterior versus posterior compartment. Anterior Omb is required to stabilize the compartment boundary in the plane of the epithelium, posterior Omb stabilizes the normal apico-basal cell properties at the A/P boundary. Regional differences also exist in Omb function in medial versus lateral wing disc: Medially, Omb represses proliferation, laterally it is stimulated by Omb. So far, it is not known how Omb realizes these functions molecularly. Using different experimental approaches we have identified numerous genes that are controlled by Omb, most of them probably indirectly. With this grant application we want to conclude work on four enhancers, each of which controls an aspect of the expression of the respective gene (mirror, hedge-hog, invected, vestigial). These genes are relatively high up in the hierarchy of wing development. We want to establish, how these enhancers are regulated by Omb, thus facilitating identification of en-hancers in additional genes.

• DFG Programme: Research Grants