BIOLOGICAL OVERVIEW

Adult mechanosensory bristles consist of four cells: two cells of neural derivation (neuron and glial or thecogen cells), and two support cells ( a socket cell [tormogen] and a shaft cell [trichogen]). These four cells are derived from a single precursor called the sensory organ precursor (SOP). Mutations in musashi and numb both result in an increase in the ratio of support cells, at the expense of neural cells. Mutation of a third gene, tramtrack, results in the opposite phenotype: the transformation of socket and shaft cells to neuron and glial cells. Ectopic expression of ttk has just the opposite effect: the transformation of neuron and glial cells into socket and shaft cells. Numb protein is asymmetrically distributed to neural precursor cells in the first division of the SOP, and Numb targets tramtrack, which then acts as a repressor of support cell fate in neural and glial progeny (Rhyu, 1994 and Guo, 1995). A double-shaft phenotype is abundant in musashi mutants, giving the gene its name -- typically, samurai warriors used only one sword; however, the famed artist-samurai Musashi Miyamoto (1584-1685) originated a style of fighting using two swords simultaneously (Nakamura, 1994).

Where does Musashi fit in the pathway that genetically controls mechanosensory bristle cell fate? MSI is a putative RNA binding protein. Analysis of the mutant phenotypes suggests that MSI acts at two levels. At the first level, the progeny of the SOP are distinguished or earmarked as being either neuron/glial precursors or shaft/socket precursor cells. At a second and later stage, the progeny of the shaft/socket cells are distinguished as being either shaft or socket cell precursors. Failure of Musashi action results in an excess of shaft and socket precursors at the expense of neuron and glial cells in the first instance, and an excess of shaft cells at the expense of socket cells in the second instance (Nakamura, 1994).

Because Musashi is nuclear, it is thought that it does not function to regulation translation, stability or subcellular localization of mRNA. Instead Musashi may regulate target mRNAs at the level of mRNA processing. Many nuclear RNA binding proteins bind pre-mRNA (high molecular weight nuclear RNAs also known as hnRNAs) and either facilitate or hinder the interaction of these hnRNAs with other components that are necessary for processing hnRNAs. The function of only a few RNA binding proteins are understood in great detail The best-characterized examples are the Drosophila Sex Lethal and transformer-2 proteins. It has been proposed that MSI controls sensillum development by regulating target genes posttranscriptionally (Nakamura, 1994).

It is also possible that MSI is required for processing Numb mRNA in the SOP. Equally likely is an involvement in processing Tramtrack mRNA. There are two alternatively spliced Tramtrack transcripts differing in alternative sets of zinc fingers as well as use of different polyadenylation signals (Harrison, 1990). It is possible that Musashi regulates Tramtrack pre-mRNA splicing, controlling the ratio of alternatively spliced products (Nakamura, 1994).

Expression of murine Musashi homolog, m-Msi-1, shows a pattern complementary to that of another mammalian RNA-binding protein, Hu (a mammalian homolog of the Drosophila neuron-specific RNA binding protein ELAV), which is exclusively expressed in postmitotic neurons in the CNS. It is possible that m-Msi-1 and Hu have distinct roles in neurogenesis that are relevant to those of Drosophila MSI and ELAV, respectively (Sakakibara, 1996).

GENE STRUCTURE

Bases in 5' UTR - 251

Exons - 3

Bases in 3' UTR - 1666

PROTEIN STRUCTURE

Amino Acids - 606

Structural Domains

MSI is homologous to RNA-binding proteins (RBPs). Many RBPs contain a conserved sequence of 80-90 amino acids, termed an RNA-binding domain (RBD) that includes two short highly conserved motifs called RNP-1 and RNP-2. The MSI protein contains two RBDs (each with two RNPs). One of the gene products most homologous to MSI is a Xenopus nervous system-specific putative RBP, NRP-1, as well as another Xenopus putative RBP, XRP-1. Each is 60% identical to MSI in the RBDs. MSI also contains amino acids in the RBDs about 50% and 42% identical (respectively) to two heterogeneous nuclear ribonucleoprotein particle (hnRNP) proteins: human hnRNP A/B protein and Drosophila HRP-40. The two MSI RBDs differ significantly in sequence. Outside of RNP-1 and RNP-2, the two RBDs are only 33% identical to one another. MSI contains two regions of 85 and 179 amino acids that are rich (about 45%) in alanine and glutamine residues. Alanine/glutamine-rich regions are also present in the Drosophila nervous system-enriched putative RBPs: ELAV and Couch potato (Nakamura, 1994).

date revised: 5 FEB 97 

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