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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References
Horvitz, H. R. & Herskowitz, I. Mechanisms of asymmetric cell division: two Bs or not two Bs, that is the question. Cell 68, 237–255 (1992).
Jan, Y. N. & Jan, L. Y. Asymmetric cell division. Nature 392, 775–778 (1998).
Guo, M., Bier, E., Jan, L. Y. & Jan, Y. N. tramtrack acts downstream of numb to specify distinct daughter cell fates during asymmetric cell divisions in the Drosophila PNS. Neuron 14, 913–925 (1995).
Giesen, K. et al. Glial development in the Drosophila CNS requires concomitant activation of glial and repression of neuronal differentiation genes. Development 124, 2307–2316 (1997).
Nakamura, M., Okano, H., Blendy, J. A. & Montell, C. Musashi, a neural RNA-binding protein required for Drosophila adult external sensory organ development. Neuron 13, 67–81 (1994).
Gho, M., Bellaiche, Y. & Francois, S. Revisiting the Drosophila microchaete lineage: a novel intrinsically asymmetric cell division generates a glial cell. Development 126, 3573–3584 (1999).
Reddy, G. V. & Rodrigues, V. A glial cell arises from an additional division within the mechanosensory lineage during development of the microchaete on the Drosophila notum. Development 126, 4617–4622 (1999).
Hartenstein, V. & Posakony, J. W. A dual function of the Notch gene in Drosophila sensillum development. Dev. Biol. 142, 13–30 (1990).
Zeng, C., Younger-Shepherd, S., Jan, L. Y. & Jan, Y. N. Delta and Serrate are redundant Notch ligands required for asymmetric cell divisions within the Drosophila sensory organ lineage. Genes Dev. 12, 1086–1091 (1998).
Guo, M., Jan, L. Y. & Jan, Y. N. Control of daughter cell fates during asymmetric division: interaction of Numb and Notch. Neuron 17, 27–41 (1996).
Ramaekers, G. et al. Lineage and fate in Drosophila: Role of the gene tramtrack in sense organ development. Dev. Genes Evol. 207, 97–106 (1997).
Li, S., Li, Y., Carthew, R. W. & Lai, Z. C. Photoreceptor cell differentiation requires regulated proteolysis of the transcriptional repressor tramtrack. Cell 90, 469–478 (1997).
Carthew, R. W. & Rubin, G. M. seven in absentia, a gene required for specification of R7 cell fate in the Drosophila eye. Cell 63, 561–577 (1990).
Chang, H. C. Y. et al. phyllopod functions in the fate determination of a subset of photoreceptors in Drosophila. Cell 80, 463–472 (1995).
Xiong, W. C. & Montell, C. tramtrack is a transcriptional repressor required for cell fate determination in the Drosophila eye. Genes Dev. 7, 1085–1096 (1993).
Buckanovich, R. J. & Darnell, R. B. The neuronal RNA binding protein Nova-1 recognizes specific RNA targets in vitro and in vivo. Mol. Cell. Biol. 17, 3194–3201 (1997).
Hirota, Y. et al. Musashi and Seven in absentia downregulate Tramtrack through distinct mechanisms in Drosophila eye development. Mech. Dev. 87, 93–101 (1999).
Gray, N. K. & Wickens, M. Control of translation initiation in animals. Annu. Rev. Cell. Dev. Biol. 14, 399–458 (1998).
Sakakibara, S. et al. mouse-Musashi-1, a neural RNA-binding protein highly enriched in the mammalian CNS stem cell. Dev. Biol. 176, 230–242 (1996).
Johansson, C. B. et al. Identification of a neural stem cell in the adult mammalian central nervous. Cell 96, 25–34 (1999).
Gaiano, N., Nye, J. S. & Fishell, G. Radial glial identity is promoted by Notch1 signaling in the murine forebrain. Neuron 26, 395–404 (2000).
Goto, S. & Hayashi, S. Cell migration within the embryonic limb primordium of Drosophila as revealed by a novel fluorescence method to visualize mRNA and protein. Dev. Genes Evol. 207, 194–198 (1997).
Spana, E. P. & Doe, C. Q. The prospero transcription factor is asymmetrically localized to the cell cortex during neuroblast mitosis in Drosophila. Development 121, 3187–3195 (1995).
Blochlinger, K., Bodmer, R., Jan, L. Y. & Jan, Y. N. Patterns of expression of cut, a protein required for external sensory organ development in wild-type and cut mutant Drosophila embryos. Genes Dev. 4, 1322–1331 (1990).
Ghysen, A. & O'Kane, C. Neural enhancer-like elements as specific cell markers in Drosophila. Development 105, 35–52 (1989).
Jacobsen, T. L., Brennan, K., Arias, A. M. & Muskavitch, M. A. Cis-interactions between Delta and Notch modulate neurogenic signalling in Drosophila. Development 125, 4531–4540 (1998).
Jin, M. H., Sawamoto, K., Ito, M. & Okano, H. The interaction between the Drosophila secreted protein Argos and the epidermal growth factor receptor inhibits dimerization of the receptor and binding of secreted spitz to the receptor. Mol. Cell. Biol. 20, 2098–2107 (2000).
Bunch, T. A., Grinblat, Y. & Goldstein, L. S. Characterization and use of the Drosophila metallothionein promoter in cultured Drosophila melanogaster cells. Nucleic Acids Res. 16, 1043–1061 (1988).
Gho, M., Lecourtois, M., Geraud, G., Posakony, J. W. & Schweisguth, F. Subcellular localization of Suppressor of Hairless in Drosophila sense organ cells during Notch signalling. Development 122, 1673–1682 (1996).
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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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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DOI: https://doi.org/10.1038/35075094
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