RNA-Binding Protein Musashi2: Developmentally Regulated Expression in Neural Precursor Cells and Subpopulations of Neurons in Mammalian CNS

Abstract

Musashi1 (Msi1) is a mammalian neural RNA-binding protein highly enriched in neural precursor cells that are capable of generating both neurons and glia during embryonic and postnatal CNS development. Here, we identified Musashi2 (Msi2), a novel mammalian RNA-binding protein that exhibits high sequence similarity to Msi1. The Msi2 transcript appeared to be distributed ubiquitously in a wide variety of tissues, consistent with the mRNA distribution of its Xenopus homolog, xrp1. However, the present study revealed cell type-specific and developmentally regulated expression of Msi2 in the mammalian CNS. Interestingly, Msi2 was expressed prominently in precursor cells in the ventricular zone and subventricular zone with the same pattern as Msi1 throughout CNS development. In the postnatal and adult CNS, this concurrent expression of Msi2 and Msi1 was seen in cells of the astrocyte lineage, including ependymal cells, a possible source for postnatal CNS stem cells. During neurogenesis, the expression of both Msi2 and Msi1 was lost in most postmitotic neurons, whereas Msi2 expression persisted in a subset of neuronal lineage cells, such as parvalbumin-containing GABA neurons in the neocortex and neurons in several nuclei of the basal ganglia. Msi2 may have a unique role that is required for the generation and/or maintenance of specific neuronal lineages. Furthermore, in vitro studies showed that Msi2 and Msi1 have similar RNA-binding specificity. These two RNA-binding proteins may exert common functions in neural precursor cells by regulating gene expression at the post-transcriptional level.

Screening for mammalian neural genes via fluorescence-activated cell sorter purification of neural precursors from Sox1 - gfp knock-in mice

“…In each case, the sequence can be linked to the identified gene via a contiguous assembly of expressed sequences. The discovery of additional 3Ј UTR sequences is consistent with the fact that a Musashi2 (Msi2h) 3Ј UTR probe detects a 7.1-kb transcript and suggests that the original 2.3-kb Msi2h cDNA sequence (AB056103) is incomplete (30). We also noted that the first 513 base pairs of the original Msi2h cDNA sequence do not align with other Msi2h ESTs or the human MSI2 sequence.…”

“…We have been able to identify three of the ESTs as corresponding to Musashi2, Sox11, and Hrmt1l3. Musashi2 has previously been described as ubiquitously expressed based on Northern analyses of adult tissues (30). However, our in situ hybridization data show that this gene is preferentially expressed in neural tissue in the fetus.…”

“…In fact, this presumed 5Ј UTR sequence has a 100% match with a genomic sequence on mouse chromosome 1, suggesting that the original cDNA is a hybrid of two clones. Msi2h is thought to play a role in the maintenance and proliferation of CNS precursor cells (30,31).…”

Musashi-2 promotes migration and invasion in bladder cancer via activation of the JAK2/STAT3 pathway

“…5 The Msi2 gene is located at chromosome 17q22 and has a sequence length of 987 bp. 6 As a RNA-binding protein, Msi2 is linked to stem cells and contribute to asymmetric cell division control, germ and somatic stem cell function, and cell fate determination in a number of tissues.…”

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

“…R ecent studies have shown that the Musashi (Msi) family of RNA-binding translational repressors is expressed in proliferative cells of the mammalian central nervous system (1,2), intestine (3), and stomach (4), leading to the proposal that Msi proteins are stem cell markers (5). Despite these observations, a functional requirement for Msi within stem cells has not been demonstrated, largely because of an inability to distinguish stem cells from their immediate daughter cells.…”