Translational repression determines a neuronal potential in Drosophila asymmetric cell division

Asymmetric cell division is a fundamental strategy for generating cellular diversity during animal development(1). Daughter cells manifest asymmetry i n their differential gene expression. Transcriptional regulation of this pr ocess has been the focus of many studies, whereas cell-type-specific 'trans lational' regulation has been considered to have a more minor role. During sensory organ development in Drosophila, Notch signalling directs the asymm etry between neuronal and non-neuronal lineages(2), and a zinc-finger trans criptional repressor Tramtrack69 (TTK69) acts downstream of Notch as a dete rminant of non-neuronal identity(3,4). Here we show that repression of TTK6 9 protein expression in the neuronal lineage occurs translationally rather than transcriptionally. This translational repression is achieved by a dire ct interaction between cis-acting sequences in the 3' untranslated region o f ttk69 messenger RNA and its trans-acting repressor, the RNA-binding prote in Musashi (MSI)(5). Although msi can act downstream of Notch, Notch signal ling does not affect MSI expression. Thus, Notch signalling is likely to re gulate MSI activity rather than its expression. Our results define cell-typ e-specific translational control of ttk69 by MSI as a downstream event of N otch signalling in asymmetric cell division.