musashi


DEVELOPMENTAL BIOLOGY

Embryonic, Larval and Adult

musashi is expressed maternally. Once the nervous system develops, staining is restricted to neurons in both the CNS and PNS. Staining is spatially localized predominantly to neurons in many larval tissues. In the adult head, highest levels are apparent in the laminal portion of the optic lobe, in the brain and in the antenna.

In the notum, four progeny of the sensory organ precursor (SOP) appear around 17-19 hours after puparium formation (apf) in microchaetae and around 8-12 hr apf in macrochaetae. In both macrochaetae and microchaetae, the SOPs as well as both second-order precursors and all four final progeny express musashi. At later stages of macrochaetae development, the neural and glial cell pair show the highest levels of staining (Nakamura, 1994).

Effects of mutation or deletion

Wild-type macrochaetae and microchaetae contain a single shaft and socket pair (the two support-type, non-neural cells of the sensillum). Mutant bristles consist of extra support cells, at the expense of neural/glial components. Many mutant bristles have two shaft cells and one socket cell, or two shafts and two sockets, or one shaft and two sockets, or no shaft and two sockets.

In the mutant notum, about half of the microchaetae are missing. These mutant microchaetae, which are missing neurons, each contain one or two extra-large support precursor cells. In addition, virtually all the microchaetae with extra supporting cells lack neurons. Nearly half of the mutant macrochaeta that do not contain a wild-type component of two outer support cells and one neuron and one glial cell contain four outer support cells and no neuron or glial cell. In macrochaetae, however, there is not a strict correlation between the presence of extra supporting cells and the absence of neurons. However, mutant macrochaetae with additional support cells frequently have one or more neurons but do not typically contain glial cells (Nakamura, 1994)

The RNA-binding protein Musashi is required intrinsically to maintain stem cell identity

A key goal of regenerative medicine is an understanding of the genetic factors that define the properties of stem cells. However, stem cell research in mammalian tissue has been hampered by a paucity of stem cell-specific markers. Although increasing evidence suggests that members of the Musashi (Msi) family of RNA-binding proteins play important functions in progenitor cells, it remains unclear whether there is a stem cell-autonomous requirement for Msi because of an inability to distinguish stem cells from early-lineage cells in mammalian tissues. In this study, using the Drosophila testis as a model system for the study of stem cell regulation, specific evidence is shown for a cell-autonomous requirement for Msi family proteins in regulating stem cell differentiation, leading to the identification of an RNA-binding protein required for spermatogonial stem cell maintenance. Loss of Msi function disrupts the balance between germ-line stem cell renewal and differentiation, resulting in the premature differentiation of germ-line stem cells. Moreover, although Msi is expressed in both somatic and germ cells, Msi function is required intrinsically in stem cells for maintenance of stem cell identity. A requirement was also required for Msi function in male meiosis, revealing that Msi has distinct roles at different stages of germ cell differentiation. The complementary expression patterns are described of the murine Msi paralogues Msi1 and Msi2 during spermatogenesis, which support the idea of distinct, evolutionarily conserved roles of Msi (Siddall, 2006; full text of article).


REFERENCES

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Barbouti, A., et al. (2003). A novel gene, MSI2, encoding a putative RNA-binding protein is recurrently rearranged at disease progression of chronic myeloid leukemia and forms a fusion gene with HOXA9 as a result of the cryptic t(7;17)(p15;q23). Cancer Res. 63(6): 1202-6. 12649177

Cuadrado, A., Garcia-Fernandez, L. F., Imai, T., Okano, H. and Munoz A. (2000). Regulation of tau RNA maturation by thyroid hormone is mediated by the neural RNA-binding protein musashi-1. Mol. Cell Neurosci. 20(2): 198-210. 12093154 p>Guo, M., Bier, E., Jan, L.Y. and Jan, Y.N. (1995). tramtrack acts downstream of numb to specify distinct daughter cell fates during asymmetric cell divisions in the Drosophila PNS. Neuron 14(5): 913-25. 7748559

Harrison, S.D. and Travers, A.A. (1990). The tramtrack gene encodes a Drosophila finger protein that interacts with the ftz transcriptional regulatory region and show a novel embryonic expression pattern. EMBO J. 9(1): 207-216. 2104801

Hirota, Y., et al. (1999). Musashi and Seven in absentia downregulate Tramtrack through distinct mechanisms in Drosophila eye development. Mech. Dev. 87: 93-101. 10495274

Imai, T., et al. (2001). The neural RNA-binding protein Musashi1 translationally regulates mammalian numb gene expression by interacting with its mRNA. Mol. Cell. Biol. 21(12): 3888-900. 11359897

Ishizuya-Oka, A., Shimizu, K., Sakakibara, S., Okano, H. and Ueda, S. (2003). Thyroid hormone-upregulated expression of Musashi-1 is specific for progenitor cells of the adult epithelium during amphibian gastrointestinal remodeling. J. Cell Sci. 116(Pt 15): 3157-64. 12799417

Kanemura, Y., et al. (2001). Musashi1, an evolutionarily conserved neural RNA-binding protein, is a versatile marker of human glioma cells in determining their cellular origin, malignancy, and proliferative activity. Differentiation 68(2-3): 141-52. 11686236

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Murphy, D., Cieply, B., Carstens, R., Ramamurthy, V. and Stoilov, P. (2016). The Musashi 1 controls the splicing of photoreceptor-specific exons in the vertebrate retina. PLoS Genet 12: e1006256. PubMed ID: 27541351

Nakamura, M, et al. (1994). Musashi, a neural RNA-binding protein required for Drosophila adult external sensory organ development. Neuron 13: 67-81. 8043282

Okabe, M., et al. (2001). Translational repression determines a neuronal potential in Drosophila asymmetric cell division. Nature 411: 94-98. 11333984

Rhyu, M.S., et al. (1994). Asymmetric distribution of numb protein during division of the sensory organ precursor cell confers distinct fates to daughter cells. Cell 76: 477-491. 8313469

Sakakibara, S., et al. (1996). Mouse-Musashi-1, a neural RNA-binding protein highly enriched in the mammalian CNS stem cell. Dev. Biol. 176: 230-242. 8660864

Sakakibara, Si. and Okano, H. (1997). Expression of neural RNA-binding proteins in the postnatal CNS: implications of their roles in neuronal and glial cell development. J. Neurosci. 17(21): 8300-8312. 9334405

Sakakibara, S.-i., et al. (2001). RNA-binding protein Musashi2: Developmentally regulated expression in neural precursor cells and subpopulations of neurons in mammalian CNS. J. Neurosci. 21(20): 8091-8107. 11588182

Sakakibara, S., et al. (2002). RNA-binding protein Musashi family: roles for CNS stem cells and a subpopulation of ependymal cells revealed by targeted disruption and antisense ablation. Proc. Natl. Acad. Sci. 99(23): 15194-9. 12407178

Saunders, P. T., et al. (2002). RNA binding protein Musashi1 is expressed in sertoli cells in the rat testis from fetal life to adulthood. Biol. Reprod. 66(2): 500-7. 11804968

Shibata, S., Umei, M., Kawahara, H., Yano, M., Makino, S. and Okano, H. (2012). Characterization of the RNA-binding protein Musashi1 in zebrafish. Brain Res 1462: 162-173. PubMed ID: 22429745

Siddall, N. A., McLaughlin, E. A., Marriner, N. L. and Hime, G. R. (2006). The RNA-binding protein Musashi is required intrinsically to maintain stem cell identity. Proc. Natl. Acad. Sci. 103(22): 8402-7. 16717192

Toda, M., et al. (2001). Expression of the neural RNA-binding protein Musashi1 in human gliomas. Glia 34(1): 1-7. 11284014

Yoda, A., Sawa, H. and Okano, H. (2000). MSI-1, a neural RNA-binding protein, is involved in male mating behaviour in Caenorhabditis elegans. Genes Cells 5(11): 885-895. 11122376

Zearfoss, N. R., Deveau, L. M., Clingman, C. C., Schmidt, E., Johnson, E. S., Massi, F. and Ryder, S. P. (2014). A conserved three-nucleotide core motif defines Musashi RNA-binding specificity. J Biol Chem 289(51):35530-41. PubMed ID: 25368328


musashi: Biological Overview | Evolutionary Homologs | Regulation | Developmental Biology | Effects of Mutation

date revised: 5 February 2015 

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