Abstract
The Mrj co-chaperone is expressed throughout the mouse conceptus, yet its requirement for placental development has prohibited a full understanding of its embryonic function. Here, we show that Mrj(-/-) embryos exhibit neural tube defects independent of the placenta phenotype, including exencephaly and thin-walled neural tubes. Molecular analyses revealed fewer proliferating cells and a down-regulation of early neural progenitor (Pax6, Olig2, Hes5) and neuronal (Nscl2, SCG10) cell markers in Mrj(-/-) neuroepithelial cells. Furthermore, Mrj(-/-) neurospheres are significantly smaller and form fewer secondary neurospheres indicating that Mrj is necessary for self-renewal of neural stem cells. However, the molecular function of Mrj in this context remains elusive because Mrj does not colocalize with Bmi-1, a self-renewal protein. Furthermore, unlike in Mrj(-/-) placentas, intermediate filament-containing aggregates do not accumulate in Mrj(-/-) neuroepithelium, ruling out nestin as a substrate for Mrj. Regardless, Mrj plays an important role in neural stem cell self-renewal.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biomarkers / metabolism
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Body Patterning / physiology
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Cell Differentiation / physiology
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Cell Proliferation
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Embryo, Mammalian* / abnormalities
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Embryo, Mammalian* / anatomy & histology
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Embryo, Mammalian* / physiology
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Epithelium / anatomy & histology
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Epithelium / physiology
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Gestational Age
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HSP40 Heat-Shock Proteins / genetics
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HSP40 Heat-Shock Proteins / metabolism*
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Intermediate Filament Proteins / genetics
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Intermediate Filament Proteins / metabolism
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Mice
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Mice, Knockout
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Molecular Chaperones / genetics
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Molecular Chaperones / metabolism*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Nestin
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Neural Tube / anatomy & histology
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Neural Tube / metabolism
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Neurons / cytology
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Neurons / physiology*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Polycomb Repressive Complex 1
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Stem Cells / cytology
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Stem Cells / physiology*
Substances
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Biomarkers
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Bmi1 protein, mouse
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Dnajb6 protein, mouse
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HSP40 Heat-Shock Proteins
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Intermediate Filament Proteins
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Molecular Chaperones
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Nerve Tissue Proteins
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Nes protein, mouse
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Nestin
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Nuclear Proteins
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Proto-Oncogene Proteins
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Repressor Proteins
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Polycomb Repressive Complex 1