title: Translational repression determines a neuronal potential in Drosophila asymmetric cell division.
abstract: Asymmetric cell division is a fundamental strategy for generating cellular diversity during animal development. Daughter cells manifest asymmetry in their differential gene expression. Transcriptional regulation of this process has been the focus of many studies, whereas cell-type-specific 'translational' regulation has been considered to have a more minor role. During sensory organ development in Drosophila, Notch signalling directs the asymmetry between neuronal and non-neuronal lineages, and a zinc-finger transcriptional repressor Tramtrack69 (TTK69) acts downstream of Notch as a determinant of non-neuronal identity. Here we show that repression of TTK69 protein expression in the neuronal lineage occurs translationally rather than transcriptionally. This translational repression is achieved by a direct interaction between cis-acting sequences in the 3' untranslated region of ttk69 messenger RNA and its trans-acting repressor, the RNA-binding protein Musashi (MSI). Although msi can act downstream of Notch, Notch signalling does not affect MSI expression. Thus, Notch signalling is likely to regulate MSI activity rather than its expression. Our results define cell-type-specific translational control of ttk69 by MSI as a downstream event of Notch signalling in asymmetric cell division.
authors.affiliation: Division of Developmental Genetics, National Institute of Genetics, and Department of Genetics, Graduate University for Advanced Studies, 1111 Yata, Mishima, Shizuoka 411-8540, Japan. maokabe@lab.nig.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Okabe
authors.forename: T
authors.initials: T
authors.lastname: Imai
authors.forename: M
authors.initials: M
authors.lastname: Kurusu
authors.forename: Y
authors.initials: Y
authors.lastname: Hiromi
authors.forename: H
authors.initials: H
authors.lastname: Okano
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002455:Cell Division; D002460:Cell Line; D019070:Cell Lineage; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D011485:Protein Binding; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000502:physiology; D051880:Receptors, Notch; D012097:Repressor Proteins / Q000235:genetics* / Q000502:physiology
chemical_list: D020413:3' Untranslated Regions; D029721:Drosophila Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; C088623:msi protein, Drosophila; C075878:ttk protein, Drosophila