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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 development1. 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 lineages2, and a zinc-finger transcriptional repressor Tramtrack69 (TTK69) acts downstream of Notch as a determinant of non-neuronal identity3,4. 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)5. 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.

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Figure 1: Non-neuronal lineage is determined by TTK69.
Figure 2: TTK69 is negatively regulated by MSI.
Figure 3: MSI inhibits translation of ttk69 mRNA by binding to its 3′UTR.
Figure 4: MSI acts downstream to Notch.

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Acknowledgements

We thank M. Nakamura, Y. N. Jan, C. Montell, S. Hayashi, A. Travers, C. Q. Doe and the Developmental Studies Hybridoma Bank, University of Iowa, for fly strains and/or DNA clones and antibodies for fly strains. We are grateful to K. Tei and D. Yamamoto for advice on the translation assay. We also thank M. Nakamura, S. Goto, M. Jindra and all members of the Okano, Hiromi, Hotta and Hayashi laboratories for helpful discussions. This work was supported by grants from the ministry of Education, Science, Sports, and Culture of Japan, and Japan Science and Technology Corporation.

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Correspondence to Masataka Okabe.

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Okabe, M., Imai, T., Kurusu, M. et al. Translational repression determines a neuronal potential in Drosophila asymmetric cell division. Nature 411, 94–98 (2001). https://doi.org/10.1038/35075094

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