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Musashi: a translational regulator of cell fate

Hideyuki Okano1,*, Takao Imai1 and Masataka Okabe2

1 Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
2 Department of Developmental Genetics, National Institute of Genetics, and Department of Genetics, Graduate University for Advanced Studies, 1111 Yata, Mishima, Shizuoka 411-8540, Japan



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  		Fig. 1. (A) The Drosophila Musashi protein. Musashi contains two RNA-recognition motifs (RRM). RNP-1 and RNP-2 are conserved amino acid sequences that are commonly contained in RRM-type RNA-binding domains. (B) The Drosophila msi mutant phenotype. The left panels show the external bristle phenotype by light microscopy; the central panels show the strucure of the adult mechanosensory organ of the indicated genotypes; the right panels show the mechanosensory bristle cell lineage of the indicated genotypes. Upper panels, wild-type. Lower panels, msi1 mutant. Abbreviations: G, Glia; N, Neuron; Sf, shaft cell; Sh, Sheath cell; So, Socket cell; SOP, sensory organ precursor cell.

 


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  		Fig. 2. A model of asymmetric cell division based upon ttk69 translational regulation. (A) In the IIb precursor, MSI (red) prevents ttk69 mRNA (purple) from being translated into protein, whereas in the IIa precursor (non-neuronal cell; pink) TTK69 protein is translated. Why MSI does not function in the IIa precursor remains to be elucidated.

(B) In the absence of MSI protein in the msi1 mutant, the IIb precursor is transformed into a IIa precursor, thus causing the `double bristle' phenotype.

 


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  		Fig. 3. A model of mammalian Musashi1 function in the regulation of the Notch1 signalling in mammals. (A) m-Numb blocks activation of the Notch signal (blocking cleavage and/or nuclear translocation with RBP-J{kappa}, among other events) by Notch ligands (Delta and Jagged), which are expressed in neighboring cells. (B) In Musashi1-expressing immature cells, mammalian Musashi1 activates Notch1 signaling through the translational repression of m-Numb. This potentiation of Notch1 signal by Musashi1 should maintain the immature proliferation status of cells expressing Musashi1. A vertical arrowhead shows the Notch1 intracellular cleavage cite.

 




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