Proliferation and differentiation of rat neuroepithelial precursor cells in vivo

Frederiksen, Kristen; McKay, Ronald D.G.

doi:10.1523/jneurosci.08-04-01144.1988

Cited by 532 publications

(326 citation statements)

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“…With continued passage, INK4a-ARF −/− and CDK4-immortalized cultures displayed a polygonal, flat morphology characteristic of cultured astrocytes and lost GFAP expression, as observed with astrocytes immortalized by other techniques (Bernard et al 1994;Frisa et al 1994). All cells in both populations expressed large amounts of nestin, consistent with a neuroectodermal origin (Frederiksen and McKay 1988). Very large nestin-positive cells were found in both the wild-type and cdk4-immortalized populations; in contrast, the INK4a-ARF −/− cells were primarily small and morphologically immature.…”

Section: Loss Of Ink4a-arf and Overexpression Of Cdk4 Both Immortalizmentioning

confidence: 52%

Modeling mutations in the G₁ arrest pathway in human gliomas: overexpression of CDK4 but not loss of INK4a–ARF induces hyperploidy in cultured mouse astrocytes

et al. 1998

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Nearly all human gliomas exhibit alterations in one of three genetic loci governing G 1 arrest: INK4a-ARF, CDK4, or RB. To discern the roles of CDK4 amplification and INK4a-ARF loss in gliomagenesis, we compared the behavior of astrocytes lacking a functional INK4a-ARF locus with astrocytes overexpressing CDK4. Either a deficiency of p16 INK4a and p19 ARF or an increase in Cdk4 allows cultured astrocytes to grow without senescence. Astrocytes overexpressing CDK4 grow more slowly than INK4a-ARF-deficient astrocytes and convert to a tetraploid state at high efficiency; in contrast, INK4a-ARF-deficient cells remain pseudodiploid, consistent with properties observed in human gliomas with corresponding lesions in these genes. Received July 20, 1998; revised version accepted October 14, 1998. Over half of high-grade human gliomas lack a functional INK4a-ARF locus (Jen et al. 1994;Schmidt et al. 1994) and hence can produce neither p16 INK4a nor p19 ARF , the two proteins encoded by this locus (Quelle et al. 1995). Most of the remaining gliomas either lack the RB gene or demonstrate a 10-to 100-fold amplification of the CDK4 locus (He et al. 1994(He et al. , 1995Ichimura et al. 1996). We are developing animal models for gliomagenesis in hopes of understanding these patterns and discerning the contributions made to tumor formation by each abnormality . We have taken advantage of two genetic alterations in mice: disruption of the INK4a-ARF locus by targeted mutation (Serrano et al. 1996) and astrocyte-specific expression of a transgene encoding TVA, the receptor for subgroup A avian leukosis viruses (ALV) (Holland and Varmus 1998). Production of TVA molecules by these cells makes them susceptible to infection by RCAS vectors carrying coding domains for CDK4 and other genes .We have used this gene transfer system to investigate the effects of INK4a-ARF loss and CDK4 overexpression in astrocyte cell culture and to determine whether similarities exist between the cultured cells and human gliomas with similar abnormalities. Results and Discussion Loss of INK4a-ARF and overexpression of CDK4 both immortalize astrocyte culturesTo compare the growth properties of INK4a-ARF-deficient and CDK4-overexpressing astrocytes, we subjected appropriately selected cultures to repeated passage at standard density and counted the number of cells at each passage. Astrocytes overexpressing CDK4 were prepared by infecting primary brain cultures from Gtv-a mice [carrying a tv-a transgene under the control of the astrocytespecific glial fibrillary acidic protein (GFAP) promoter] with an RCAS vector carrying the human CDK4 cDNA (RCAS-cdk4). Cultures of INK4a-ARF-deficient astrocytes were prepared by infecting primary brain cell cultures from Gtv-a transgenic; INK4a-ARF −/− mice with an RCAS vector bearing the puro-R gene (RCAS-puro) ) and selecting for resistance to puromycin. Parallel cultures were prepared by infecting brain cells from Gtv-a transgenic mice with RCAS vectors carrying the alkaline phosphatase (AP) or the basic fibroblast grow...

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Section: Loss Of Ink4a-arf and Overexpression Of Cdk4 Both Immortalizmentioning

confidence: 52%

Modeling mutations in the G₁ arrest pathway in human gliomas: overexpression of CDK4 but not loss of INK4a–ARF induces hyperploidy in cultured mouse astrocytes

et al. 1998

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“…As the cell number increases, proliferation is confined primarily to the ventricular zone, whereas postmitotic differentiating neurons migrate toward the pial surface (Frederiksen and McKay, 1988;Rakic, 1988). The polarized distribution of the dividing and differentiating cells within the neuroepithelium may be caused by the uneven partitioning of key cellular components during cell divisions of the progenitor cells.…”

Section: Discussionmentioning

confidence: 99%

Nestin Promotes the Phosphorylation-dependent Disassembly of Vimentin Intermediate Filaments During Mitosis

Chou

Khuon

Herrmann

et al. 2003

MBoC

175

153

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The expression of the intermediate filament (IF) protein nestin is closely associated with rapidly proliferating progenitor cells during neurogenesis and myogenesis, but little is known about its function. In this study, we examine the effects of nestin expression on the assembly state of vimentin IFs in nestin-free cells. Nestin is introduced by transient transfection and is positively correlated with the disassembly of vimentin IFs into nonfilamentous aggregates or particles in mitotic but not interphase cells. This nestin-mediated disassembly of IFs is dependent on the phosphorylation of vimentin by the maturation/M-phase–promoting factor at ser-55 in the amino-terminal head domain. In addition, the disassembly of vimentin IFs during mitosis appears to be a unique feature of nestin-expressing cell types. Furthermore, when the expression of nestin is downregulated by the nestin-specific small interfering RNA in nestin-expressing cells, vimentin IFs remain assembled throughout all stages of mitosis. Previous studies suggest that nonfilamentous vimentin particles are IF precursors and can be transported rapidly between different cytoplasmic compartments along microtubule tracks. On the basis of these observations, we speculate that nestin may play a role in the trafficking and distribution of IF proteins and potentially other cellular factors to daughter cells during progenitor cell division

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“…Interestingly, both of these sources of dividing m-Msi-1-positive cells also expressed another intermediate filament protein, nestin (Fig. 8 E,F ), which is a well defined marker for neural precursors or stem cells during normal development of the C NS (Hockfield and McKay, 1985;Frederiksen and McKay, 1988;Lendahl et al, 1990;Zimmerman et al, 1994). Although the uninjured adult forebrain had weak nestin immunoreactivity, marked induction of nestin was observed 4 d after injury in both regions adjacent to the injury site (Fig.…”

Section: Changes In M-msi-1 Immunoreactivity After Injurymentioning

confidence: 95%

Expression of Neural RNA-Binding Proteins in the Postnatal CNS: Implications of Their Roles in Neuronal and Glial Cell Development

1997

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There is an increasing interest in the role of RNA-binding proteins during neural development. Mouse-Musashi-1 (m-Msi-1) is a mouse neural RNA-binding protein with sequence similarity to Drosophila musashi (d-msi), which is essential for neural development. m-Msi-1 is highly enriched in neural precursor cells that are capable of generating both neurons and glia during embryonic CNS development. The present study characterized m-Msi-1-expressing cells in the postnatal and adult CNS. Postnatally, m-Msi-1 was expressed in proliferative neuronal precursors in the external granule cell layer of the cerebellum and in the anterior corner of the subventricular zone of the lateral ventricles. In gliogenesis, the persistent expression of m-Msi-1 was observed in cells of the astrocyte lineage ranging from proliferative glial precursors in the subventricular zone (SVZ) to differentiated astrocytes in the parenchyma. In addition, we showed that m-Msi-1 was still expressed in proliferating cells in the adult SVZ, which may contain neural precursor or stem cells. Another neural RNA-binding protein Hu (the mammalian homolog of a Drosophila neuronal RNAbinding protein Elav) was present in postmitotic neurons throughout the development of the CNS, and its pattern of expression was compared with that of m-Msi-1. These observations imply that these two RNA-binding proteins may be involved in the development of neurons and glia by regulating gene expression at the post-transcriptional level. Key words: RNA-binding proteins; postnatal CNS; mouseMusashi-1 (m-Msi-1); Hu; Drosophila musashi; neuronal and glial precursor cells; astrocyte lineageA number of transcription factors that f unction in the proliferation and differentiation of neural precursor cells have been identified. However, the recent discovery of neural-specific RNAbinding proteins raises the possibility that the development of neural cells from the precursors may also be regulated at the post-transcriptional level. We believe that at least two gene families are represented by the neural RNA-binding proteins found in both invertebrates and vertebrates (Okano, 1995;Sakakibara et al., 1996). One, the Elav family, includes Drosophila elav genes (Yao et al., 1993) and their mammalian homologs, the Hu genes (Szabo et al., 1991). Members of this family share extensive sequence similarity with one another, and they seem to be expressed mainly in postmitotic neurons (Okano and Darnell, 1997). The other Msi family is composed of Drosophila musashi (Nakamura et al., 1994), Xenopus laevis nrp-1 (Richter et al., 1990), and their mouse homolog mouse-musashi-1 (m-msi-1) (Sakakibara et al., 1996). d-Msi is required for the two successive asymmetric cell divisions of sensory organ precursors (Nakamura et al., 1994). In contrast to the Elav family, the members of the Msi family are expressed in the neural precursor cells at least during embryonic C NS development (Sakakibara et al., 1996). Although the molecular f unctions and the in vivo RNA targets of Msi and Elav families remain largel...

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Proliferation and differentiation of rat neuroepithelial precursor cells in vivo

Cited by 532 publications

References 30 publications

Modeling mutations in the G₁ arrest pathway in human gliomas: overexpression of CDK4 but not loss of INK4a–ARF induces hyperploidy in cultured mouse astrocytes

Modeling mutations in the G₁ arrest pathway in human gliomas: overexpression of CDK4 but not loss of INK4a–ARF induces hyperploidy in cultured mouse astrocytes

Nestin Promotes the Phosphorylation-dependent Disassembly of Vimentin Intermediate Filaments During Mitosis

Expression of Neural RNA-Binding Proteins in the Postnatal CNS: Implications of Their Roles in Neuronal and Glial Cell Development

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Proliferation and differentiation of rat neuroepithelial precursor cells in vivo

Cited by 532 publications

References 30 publications

Modeling mutations in the G1 arrest pathway in human gliomas: overexpression of CDK4 but not loss of INK4a–ARF induces hyperploidy in cultured mouse astrocytes

Modeling mutations in the G1 arrest pathway in human gliomas: overexpression of CDK4 but not loss of INK4a–ARF induces hyperploidy in cultured mouse astrocytes

Nestin Promotes the Phosphorylation-dependent Disassembly of Vimentin Intermediate Filaments During Mitosis

Expression of Neural RNA-Binding Proteins in the Postnatal CNS: Implications of Their Roles in Neuronal and Glial Cell Development

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Modeling mutations in the G₁ arrest pathway in human gliomas: overexpression of CDK4 but not loss of INK4a–ARF induces hyperploidy in cultured mouse astrocytes

Modeling mutations in the G₁ arrest pathway in human gliomas: overexpression of CDK4 but not loss of INK4a–ARF induces hyperploidy in cultured mouse astrocytes