Astrocyte Growth, Reactivity, and the Target of the Antiproliferative Antibody, TAPA

Geisert, Eldon E.; Yang, Lijuan; Irwin, Michael H.

doi:10.1523/jneurosci.16-17-05478.1996

Cited by 60 publications

(76 citation statements)

References 49 publications

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“…16,17 ) and astrocyte lineages (GFAP, TAPA-1, CD44; refs. [18][19][20]. In addition, approximately one-third of GFP -cells expressed markers associated with neural progenitors and stem cells, including nestin 21 , prominin-1 (ref.…”

Section: Non-granule Cell Precursors Proliferate In Response To Bfgfmentioning

confidence: 99%

Isolation of neural stem cells from the postnatal cerebellum

et al. 2005

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The cerebellum is critical for motor coordination and cognitive function and is the target of transformation in medulloblastoma, the most common malignant brain tumor in children. Although the development of granule cells, the most abundant neurons in the cerebellum, has been studied in detail, the origins of other cerebellar neurons and glia remain poorly understood. Here we show that the murine postnatal cerebellum contains multipotent neural stem cells (NSCs). These cells can be prospectively isolated based on their expression of the NSC marker prominin-1 (CD133) and their lack of markers of neuronal and glial lineages (lin -). Purified prominin + lin -cells form self-renewing neurospheres and can differentiate into astrocytes, oligodendrocytes and neurons in vitro. Moreover, they can generate each of these lineages after transplantation into the cerebellum. Identification of cerebellar stem cells has important implications for the understanding of cerebellar development and the origins of medulloblastoma.The cerebellum is required for motor coordination and is crucial for cognitive and affective processing 1 . These functions depend on interactions among at least six types of neurons and two types of glia 2 . Disruption of cerebellar structure and function is associated with disorders such as ataxia, autism and schizophrenia 3-5 . In addition, uncontrolled growth of cerebellar precursors results in medulloblastoma 6,7 . Elucidating the mechanisms that control the generation of cerebellar neurons and glia during normal development is critical for understanding the basis of these diseases.The cerebellum differs from most other brain regions in that it contains two distinct germinal layers: the ventricular zone (VZ), which is most active during embryonic development, and the external germinal layer (EGL), which contributes to neurogenesis after birth 2 . There is strong evidence that Purkinje cells, the major output neurons of the cerebellum, originate from the VZ and that granule cells, the most abundant interneurons, arise from the EGL. However, the origin of the other cell types in the cerebellar cortex-including astrocytes, oligodendrocytes and stellate, basket, Lugaro and Golgi interneurons-is much less clear. Tissue grafting and transplantation studies suggest that many of these cells arise from VZ progenitors that migrate into the cerebellar cortex after birth 8,9 . But whether each class of neuron and glial cell comes from a distinct progenitor or whether they all come from a common, multipotent progenitor is not known. Here we purify a population of multipotent neural stem cells from the postnatal cerebellum. We show that this population can undergo self-renewal in culture and can generate neurons, astrocytes and oligodendrocytes both in vitro and after transplantation. Our findings suggest that cerebellar neurons and glia could be generated from a common progenitor. In addition, the approach we have used may be applicable for isolating NSCs from other parts of the nervous system. RESULTS Non-g...

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Section: Non-granule Cell Precursors Proliferate In Response To Bfgfmentioning

confidence: 99%

Isolation of neural stem cells from the postnatal cerebellum

et al. 2005

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“…These cellular membranes can then contract and cause secondary retinal detachments. The reactive glial responses and the proliferation of non-neuronal cells can have serious consequences, including loss of sight.Studies in our laboratory have identified a protein, CD81, which plays a role in the response of the brain [9], spinal cord [5], and retina [10]. We originally called CD81 the target of the antiproliferative antibody.…”

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“…We have hypothesized that this CD81 molecular complex is a key element in the contact inhibition between glial cells in the brain. Antibodies directed against CD81 depress the mitotic activity of cultured cells [9,17]. Furthermore, CD81 is expressed by glial cells in the brain during the second postnatal week, a time when their mitotic activity is down-regulated [19].…”

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“…Three rats were used at each time point. A quantitative immunoblot method was similar to that previously described [9]. The protein samples were balanced and equal loads of proteins were run on 5% to 16% acrylamide gels.…”

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“…Resting microglia can become activated and, along with invading peripheral blood components, mount an inflammatory response [6]. All of these non-neuronal cells that are associated with the response of the retina to injury are known to express CD81 [5,6,9,17]. Thus, CD81 may play a critical role in different cellular responses after injury.…”

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Temporal regulation of CD81 following retinal injury in the rat

Song

Geisert

Vázquez-Chona

et al. 2003

Neuroscience Letters

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Following retinal injury, glial cells within the retina undergo a response that is characterized by the proliferation of astrocytes, Müller cells, and retinal pigment epithelial cells. CD81, a small membrane protein known to be involved in cell proliferation, is up-regulated after injury. This study focuses on the temporal regulation of CD81, relating the expression of this protein to glial fibrillary acidic protein (GFAP), the classic marker of gliosis. CD81 levels were elevated at 7 days after injury and remained elevated at 30 days after injury; GFAP was increased at 7 days and continued to increase until 30 days post injury. This association of CD81 with glial reactivity may provide a clue to the regulation of the proliferative response following retinal injury. KeywordsCD81; Glial fibrillary acidic protein; Retina; Injury; Tetraspanin; Gliosis; ProliferationThe response of the retina to trauma involves well-characterized cellular reactions [16], many of them similar to responses that occur in other parts of the central nervous system. As in the brain and spinal cord, a dramatic up-regulation of glial fibrillary acidic protein (GFAP) follows retinal injury. This up-regulation of GFAP marks reactive retinal astrocytes [12,16], which hypertrophy and increase their expression of the intermediate filament protein GFAP [3,13,18]. Müller glia and the retinal pigment epithelium (RPE), which are unique to the retina, also demonstrate characteristic responses to injury. Müller cells, like astrocytes, up-regulate GFAP. In addition, both Müller glia cells and RPE cells can proliferate to form scar tissues within the retina [14]. They also can migrate into the vitreal space, proliferate, and form cellular membranes [7], a response known as proliferative vitreoretinopathy [11]. These cellular membranes can then contract and cause secondary retinal detachments. The reactive glial responses and the proliferation of non-neuronal cells can have serious consequences, including loss of sight.Studies in our laboratory have identified a protein, CD81, which plays a role in the response of the brain [9], spinal cord [5], and retina [10]. We originally called CD81 the target of the antiproliferative antibody. As that name implies, this protein is part of a molecular complex that controls the proliferation of glial cells. We have hypothesized that this CD81 molecular complex is a key element in the contact inhibition between glial cells in the brain. Antibodies directed against CD81 depress the mitotic activity of cultured cells [9,17]. Furthermore, CD81 is expressed by glial cells in the brain during the second postnatal week, a time when their mitotic activity is down-regulated [19]. The antiproliferative role of this protein is confirmed by mice with a CD81-null mutation [10]. These CD81-null mice have very large brains containing an over abundance of astrocytes and microglia [10]. We have found that CD81 is In this study, we used the monoclonal antibody AMP1 to recognize CD81 [9]. A polyclonal antibody purchased from Li...

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Expression of rat target of the antiproliferative antibody (TAPA) in the developing brain

Sullivan

Geisert

1998

J. Comp. Neurol.

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The present study defines the expression pattern of TAPA (target of the antiproliferative antibody, also known as CD81) in the developing rat brain. TAPA is a member of the tetramembrane spanning family of proteins, and like other members of this family it appears to be associated with the stabilization of cellular contacts (Geisert et al. [1996] J. Neurosci. 16:5478-5487). On immunoblots of the brain, TAPA is present in higher levels than any other tissue examined: muscle, tendon, peripheral nerve, cartilage, liver, kidney, skin, and testicle. Immunohistochemical methods were used to define the distribution of TAPA in the brain. This protein is expressed by ependyma, choroid plexus, astrocytes, and oligodendrocytes. TAPA is dramatically upregulated during early postnatal development, at the time of glial birth and maturation. At embryonic day 18, the levels of TAPA are low, with most of the immunoreaction product being associated with the ependyma, choroid plexus, and the glia limitans. As development continues, the amount of TAPA expressed in the brain increases, and at postnatal day 14 the levels approach those of the adult. This increase in the levels of TAPA at postnatal day 14 is due to upregulation in the gray matter and white matter. Thus, TAPA is found in all glial cells, and the level of this protein correlates with their maturation.

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Astrocyte Growth, Reactivity, and the Target of the Antiproliferative Antibody, TAPA

Cited by 60 publications

References 49 publications

Isolation of neural stem cells from the postnatal cerebellum

Isolation of neural stem cells from the postnatal cerebellum

Temporal regulation of CD81 following retinal injury in the rat

Expression of rat target of the antiproliferative antibody (TAPA) in the developing brain

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