Identification of neural stem cells-specific target genes of the growth-promoting transcriptional regulator Yorkie in Drosophila melanogaster

• Applicant: Privatdozent Dr. Joachim Urban, since 5/2017
• Subject Area: Developmental Neurobiology ; Developmental Biology
• Term: from 2015 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 275997420

The aim of this research plan is to identify the stem cell-specific target genes of the transcriptional regulator Yorkie, the main effector of the highly conserved Salvador-Hippo-Warts signalling cascade (SHW) regulating growth and proliferation in virtually every tissue of invertebrates and vertebrates. The biological system we want to use are the early larval Drosophila neural stem cells, called NBs. Our recent work shows, that the SHW maintains cellular quiescence in NBs at the beginning of larval life. Loss of the core components of the SHW pathway leads to premature growth and proliferation in NBs. This system is developmentally coordinated by cell-cell contact growth inhibition mediated by transmembrane proteins Crumbs and Echinoid expressed on glial cells and NBs. Moreover, the effector of the SHW, Yorkie, is necessary and sufficient for NB growth and proliferation. Since both Yorkie and its vertebrate homology YAP/TAZ are implicated in stem cell proliferation, maintenance and pluripotency it is of immense interest to find the stem cell-specific target genes of these proteins. The approach we take is to FACS purify stem cells and to use ChIP-Sequecing on Yorkie to identify potential target genes genome-wide. Combination with mRNA-Sequencing of wild type and yorkie-mutant NBs will identify all direct Yorkie targets. After extracting the highly conserved target genes, we will functionally analyse the genes for their role during NBs reactivation, proliferation and stem cell identity maintenance. In the light of the high conservation of this pathway, the impact of the obtained results will be very important even outside the immediate field of Drosophila stem cell biology. The novel candidates will give new insights into the regulation of stem cell quiescence, reactivation, proliferation and stem cell identity maintenance.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Dr. Christian Berger, until 4/2017