Weaver mouse cerebellar granule neurons fail to migrate on wild-type astroglial processes in vitro

Hatten, Mary E.; Liem, Ronald K.H.; Mason, Carol A.

doi:10.1523/jneurosci.06-09-02676.1986

Cited by 136 publications

(60 citation statements)

References 24 publications

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“…Cultured granule cells harvested from the young cerebellum of weaver form neurites that are only about 20% of normal length (Willinger and Margolis, 1985b). The stubby neurites are characterized by uneven thickness and failure to form the cell-cell contacts necessary for successful migration (Hatten et al, 1986;Willinger and Margolis, 1985a). Delayed development has not been assessed for the midbrain's dopamine-containing neurons in weaver, but the affected neurons do appear to suffer arrested development as is seen by lack of dendritic development and failure to develop normal dopamine uptake capacity (Triarhou and Ghetti, 1989;Roffler-Tarlov et al, 1990a,b).…”

Section: Discussionmentioning

confidence: 99%

Male‐sterile phenotype of the neurological mouse mutant weaver

Harrison

Roffler-Tarlov

1994

Developmental Dynamics

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The autosomal recessive murine mutation weauer (wu) affects postnatal differentiation in at least three neuronal populations in the brain: dopamine-containing neurons in the midbrain, and granule and Purkinje cells in the cerebellum. Neuronal populations vulnerable to the actions of weaver die in the midst of development. In addition, homozygous weaver males are sterile. We show by a histological analysis of epididymides and testes that the cause of male sterility in weaver is lack of sperm. The epididymides of the adult weaver mice examined were devoid of sperm, and few seminiferous tubules in the adult weaver's testes contained elongated spermatids. Most tubules were marked by moderate to severe degeneration of the seminiferous epithelium. A developmental study showed that the mutant phenotype emerged after the third postnatal week. By postnatal day 28, the development of weaver sperm lagged behind that of the wild-type and some seminiferous tubules contained degenerating germ cells. By postnatal day 35, terminal differentiation of spermatids appeared to be arrested in many tubules and degeneration of the seminiferous epithelium was widespread. The heterozygotes were unaffected at all ages sampled. We conclude that the normal allele at the weaver locus is necessary for spermiogenesis and the maintenance of spermatogenesis. 0 1994 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Male‐sterile phenotype of the neurological mouse mutant weaver

Harrison

Roffler-Tarlov

1994

Developmental Dynamics

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“…This mouse line overexpresses ovine PrP from natural regulatory sequences under a mouse PrP 0/0 background (21). Primary culture of CGN provides a means to obtain highly enriched and homogenous populations of postmitotic neurons, which can be maintained for Ͼ1 month (26,27). Typically, cultures were mainly composed of neurons (Ͼ95%) up to 2 weeks after seeding, with 4-5% astrocytes and Ͻ1% microglial cells.…”

Section: Primary Cultures Of Mouse Cerebellar Cells Expressing Sheep mentioning

confidence: 99%

Prions can infect primary cultured neurons and astrocytes and promote neuronal cell death

Cronier

Laude

Peyrin

2004

Proc. Natl. Acad. Sci. U.S.A.

139

150

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Transmissible spongiform encephalopathies arise as a consequence of infection of the central nervous system by prions, where neurons and glial cells are regarded as primary targets. Neuronal loss and gliosis, associated with the accumulation of misfolded prion protein (PrP), are hallmarks of prion diseases; yet the mechanisms underlying such disorders remain unclear. Here we introduced a cell system based on primary cerebellar cultures established from transgenic mice expressing ovine PrP and then exposed to sheep scrapie agent. Upon exposure to low doses of infectious agent, such cultures, unlike cultures originating from PrP null mice, were found to accumulate de novo abnormal PrP and infectivity, as assessed by mouse bioassay. Importantly, using astrocyte and neuron͞astrocyte cocultures, both cell types were found capable of sustaining efficient prion propagation independently, leading to the production of proteinase K-resistant PrP of the same electrophoretic profile as in diseased brain. Moreover, contrasting with data obtained in chronically infected cell lines, late-occurring apoptosis was consistently demonstrated in the infected neuronal cultures. Our results provide evidence that primary cultured neural cells, including postmitotic neurons, are permissive to prion replication, thus establishing an approach to study the mechanisms involved in prion-triggered neurodegeneration at a cellular level.T ransmissible spongiform encephalopathies (TSE), which include Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy in cattle, and scrapie in sheep, are fatal neurodegenerative disorders caused by prions, a class of unconventional agents that targets the CNS in mammals. A hallmark of prion diseases is the accumulation of abnormal prion protein (PrP Sc ), a misfolded form of the cellular PrP (PrP c ). Transmissibility is believed to stem from the ability of the prion isoform to promote the conformational transition from PrP c to PrP Sc . Biologically distinct prion strains can propagate in a same host, presumably through the perpetuation of different specific PrP Sc conformers (1-3).Although it seems clear that neuronal dysfunction must lie at the root of the clinical disorders observed in these diseases, it is still obscure what triggers neurodegeneration and what role nonneuronal cells may play in this process. There is ample evidence to support a primary role of the neurons in prion propagation and neuropathogenesis into the CNS. Intra-or perineuronal PrP Sc deposition, spongiform vacuolation involving cell soma and processes, and neuronal loss are typical histopathological changes observed in TSE-affected brain tissues (4, 5). Transgenic mice with PrP expression specifically targeted to neurons have been obtained that turned out to be fully susceptible to prion disease (6). More recently, it was shown that an acute neuron-targeted depletion of PrP in the brain of mice with ongoing infection is able to prevent neuronal loss and progression to disease and even to reverse early spongiform chang...

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“…For glia-mediated granule neuron migration (Hatten et al, 1986), enriched glia isolated from P6 cerebella were cultured at low density. After 7 days in vitro, cultured glia were free from neuron contamination.…”

Section: Isolation Of Granule Neurons and In Vitro Migration Assaymentioning

confidence: 99%

PTEN deletion in Bergmann glia leads to premature differentiation and affects laminar organization

et al. 2005

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Development of the central nervous system is controlled by both intrinsic and extrinsic signals that guide neuronal migration to form laminae. Although defects in neuronal mobility have been well documented as a mechanism for abnormal laminar formation, the role of radial glia, which provide the environmental cues, in modulating neuronal migration is less clear. We provide evidence that loss of PTEN in Bergmann glia leads to premature differentiation of this crucial cell population and subsequently to extensive layering defects. Accordingly, severe granule neuron migration defects and abnormal laminar formation are observed. These results uncover an unexpected role for PTEN in regulating Bergmann glia differentiation, as well as the importance of time-dependent Bergmann glia differentiation during cerebellar development.

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Weaver mouse cerebellar granule neurons fail to migrate on wild-type astroglial processes in vitro

Cited by 136 publications

References 24 publications

Male‐sterile phenotype of the neurological mouse mutant weaver

Male‐sterile phenotype of the neurological mouse mutant weaver

Prions can infect primary cultured neurons and astrocytes and promote neuronal cell death

PTEN deletion in Bergmann glia leads to premature differentiation and affects laminar organization

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