title: Drosophila SETDB1 and caspase cooperatively fine-tune cell fate determination of sensory organ precursor.
abstract: Drosophila produce a constant number of mechanosensory bristles called macrochaetae (MC), which develop from sensory organ precursor (SOP) cells within a proneural cluster (PNC). However, what ensures the precise determination of SOP cells remains to be elucidated. In this study, we conducted RNAi screening in PNC for genes involved in epigenetic regulation. We identified a H3K9 histone methyltransferase, SETDB1/eggless, as a regulator of SOP development. Knockdown of SETDB1 in PNC led to additional SOPs. We further tested the relationship between SETDB1 and non-apoptotic function of caspase on SOP development. Reinforcing caspase activation by heterozygous Drosophila inhibitor of apoptosis protein 1 (DIAP1) mutation rescued ectopic SOP development caused by SETDB1 knockdown. Knockdown of SETDB1, however, had little effect on caspase activity. Simultaneous loss of SETDB1 and caspase activity resulted in further increase in MC, indicating that the two components work cooperatively. Our study suggests the fine-tuning mechanisms for SOP development by epigenetic methyltransferase and non-apoptotic caspase function.
authors.affiliation: Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Natsuki
authors.initials: N
authors.lastname: Shinoda
authors.affiliation: Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Obata
authors.affiliation: Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Liu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.|Agency for Medical Research and Development-Core Research for Evolutional Medical Science and Technology (AMED-CREST), Japan Agency for Medical Research and Development, 20F Yomiuri Shimbun Building 1-7-1 Otemachi, Chiyoda-ku, Tokyo 100-0004, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miura
mesh_terms: D000818:Animals; D020169:Caspases / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D011495:Histone-Lysine N-Methyltransferase; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism
chemical_list: C111891:DIAP1 protein, Drosophila; D029721:Drosophila Proteins; D051034:Inhibitor of Apoptosis Proteins; D011495:Histone-Lysine N-Methyltransferase; C519551:egg protein, Drosophila; D020169:Caspases