Regulators determining the identities of specific heart and somatic muscles in Drosophila

• Applicant: Professor Dr. Manfred Frasch
• Subject Area: Developmental Biology ; Evolutionary Cell and Developmental Biology (Zoology)
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 251892081

How do selector genes control specific transcriptional programs of tissue formation and which realizator genes do they activate during these processes? We aim to attack these questions by utilizing the T-box gene org-1 (Drosophila Tbx-1) as a paradigm, which functions as a muscle identity gene during embryonic development. A known function of org-1 during this process includes the activation of two other muscle identity genes, slouch and ladybird, which encode homeodomain transcription factors, as direct downstream targets in distinct subsets of muscle founder cells. These regulatory events are crucial components of the genetic program that imparts the muscle fibers with their specific characteristics. However, as is the case for other selector genes, the differentiation genes that are activated by org-1, slouch and ladybird during these events remain largely unknown.Hence, the first part of the proposed project aims to use global screens to identify genes that are activated by org-1, perhaps in combination with slouch or ladybird, as direct target genes in muscle founder cells and muscle precursors. One approach taken towards this goal is the determination of the transcriptomes of the Org-1 positive muscle cells as well as those of their Slouch and Ladybird positive subsets. A second, closely interlinked approach is the determination of the genome-wide in vivo binding sites of Org-1 during the same developmental stages as used for the transcriptome analyses. Comparisons of the flanking genes of these Org-1-associated sequences with the genes expressed preferentially in Org-1-positive cells from the transcriptome data, as well as analyses of the activities and regulation of these sequences as muscle-specific enhancer elements, are expected to provide a much clearer picture of the developmental and molecular functions of these muscle identity genes.The second part of the proposal aims to use org-1 as a tool to advance our insight into the role of muscle identity genes during adult muscle and heart development at metamorphosis, about which currently very little is known. Preliminary data suggest crucial roles of org-1 during the formation of the ventral longitudinal heart muscles and ventral abdominal somatic muscles of the adults. Our observations point to unusual de- and re-differentiation events and interesting migration processes during these developmental events. Therefore we plan to undertake imaging and genetic analyses to further characterize these developmental processes and the functions of org-1 therein, and to identify additional genes that participate in their regulation either together with org-1 or downstream of it.

• DFG Programme: Research Grants