Document Detail


RNA-binding protein Musashi family: roles for CNS stem cells and a subpopulation of ependymal cells revealed by targeted disruption and antisense ablation.
MedLine Citation:
PMID:  12407178     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Homologues of the Musashi family of RNA-binding proteins are evolutionarily conserved across species. In mammals, two members of this family, Musashi1 (Msi1) and Musashi2 (Msi2), are strongly coexpressed in neural precursor cells, including CNS stem cells. To address the in vivo roles of msi in neural development, we generated mice with a targeted disruption of the gene encoding Msi1. Homozygous newborn mice frequently developed obstructive hydrocephalus with aberrant proliferation of ependymal cells in a restricted area surrounding the Sylvius aqueduct. These observations indicate a vital role for msi1 in the normal development of this subpopulation of ependymal cells, which has been speculated to be a source of postnatal CNS stem cells. On the other hand, histological examination and an in vitro neurosphere assay showed that neither the embryonic CNS development nor the self-renewal activity of CNS stem cells in embryonic forebrains appeared to be affected by the disruption of msi1, but the diversity of the cell types produced by the stem cells was moderately reduced by the msi1 deficiency. Therefore, we performed antisense ablation experiments to target both msi1 and msi2 in embryonic neural precursor cells. Administration of the antisense peptide-nucleotides, which were designed to specifically down-regulate msi2 expression, to msi1(-/-) CNS stem cell cultures drastically suppressed the formation of neurospheres in a dose-dependent manner. Antisense-treated msi1(-/-) CNS stem cells showed a reduced proliferative activity. These data suggest that msi1 and msi2 are cooperatively involved in the proliferation and maintenance of CNS stem cell populations.
Authors:
Shin-ichi Sakakibara; Yuki Nakamura; Tetsu Yoshida; Shinsuke Shibata; Masato Koike; Hiroshi Takano; Shuichi Ueda; Yasuo Uchiyama; Tetsuo Noda; Hideyuki Okano
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2002-10-29
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  99     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-11-13     Completed Date:  2003-01-15     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  15194-9     Citation Subset:  IM    
Affiliation:
Department of Histology and Neurobiology, Dokkyo University School of Medicine, Tochigi 321-0293, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Base Sequence
DNA Primers
Disease Models, Animal
Ependyma / abnormalities*,  cytology,  physiology*
Gene Deletion
Homozygote
Hydrocephalus / genetics*,  pathology
Mice
Mice, Knockout
Models, Neurological
Mutagenesis, Insertional
Neurons / physiology*
RNA-Binding Proteins / genetics*,  metabolism*
Restriction Mapping
Reverse Transcriptase Polymerase Chain Reaction
Stem Cells / physiology*
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Msi2h protein, mouse; 0/RNA-Binding Proteins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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