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New role for radial glia
Newsdesk
Olig1 needed for remyelination Researchers in the USA and UK report that the transcription factor Olig1 is needed in the nucleus for the differentiation of oligodendrocytes in adult mice, and therefore for remyelination (Science, 2004; 306: 2111–15). The finding may have an application in the treatment of multiple sclerosis (MS). “Olig1 and a close structural homologue, Olig 2, are both expressed during the development of the nervous system”, explains US group leader Charles Stiles (Dana-Farber Cancer Institute, Boston, MA, USA). “But whereas Olig2 is essential for oligodendrocyte and neuron specification during this period, Olig1 seems not to be—in fact, no-one is sure what it does. Our work shows that Olig1 is certainly needed for any remyelination to occur.” Stiles’ team used antibodies to locate Olig1 and Olig2 during the development and repair of the nervous system
in mice. Olig2 was found in the nuclei of CNS cells at all stages of whitematter development. However, nearly all the Olig1 had moved from the nucleus to the cytoplasm by 2 weeks after birth, the developmental stage at which progenitor cells differentiate into myelin-basic-protein-positive oligodendrocytes. When the UK research group (University of Cambridge) examined mice in which demyelination had been chemically induced, Olig1 was found in the nucleus of cells in early remyelinating lesions, as well as in the remyelinating cerebral lesions in postmortem brain tissue from patients who had MS. These findings suggest that repetition of Olig1’s localisation in the nucleus as seen during development might be needed for repair. Indeed, in repaired tissue, Olig1 was again found in the cytoplasm.
“However, Olig1–/– mice—which undergo largely normal myelination during development—were unable to remyelinate”, explains Stiles. “When [we followed] oligodendrocyte maturation in demyelinated Olig1 knockout mice, the progenitors of these cells were unable to differentiate. So, it seems that although Olig1 is not needed for oligodendrocyte differentiation during development, it is required for remyelination, and it has to be located in the nucleus if the signal to mature is to be understood.” “It’s not yet clear whether there is any failure of the Olig1 system in MS that might hinder remyelination”, remarks Peter Dowling (New Jersey Medical School, East Orange, NJ, USA). “If there is, this might offer new therapeutic targets.”
Adrian Burton
New role for radial glia The recent finding that adult neural stem cells in the subventricular zone are derived from radial glia could have implications for the therapeutic use of stem cells. To test the hypothesis that radial glia in the neonatal brain produce the neurogenic astrocytes found in the adult subventricular zone, Arturo Alvarez-Buylla (Department of Neurological Surgery, University of California, San Francisco, USA) and colleagues traced the progeny of radial glia in newborn mice (Proc Natl Acad Sci USA 2004; 101: 17528–32). “We tagged a subpopulation of radial glia in the neonatal lateral ventricle and showed that these cells produce all of the major brain-cell types, including neurons, astrocytes, and oligodendrocytes”, Alvarez-Buylla told The Lancet Neurology. “More importantly, we showed that neonatal radial glia give rise to the subventricular zone astrocytes that produce neurons 80
throughout life in the adult brain.” Previous research suggested that the brain has two separate lineages: one for neurons and another for glial cells. In the late 1980s, studies in adult birds suggested that radial glia were not involved in the formation of glial cells but were the precursors of neurons, Alvarez-Buylla says. More recent studies report that radial glia in the developing brains of rodents are also stem cells, and cells with glial characteristics have been identified as the primary precursors of new neurons in adult rodents. Although these findings prompted a major conceptual shift in the understanding of cell origin in the brain, the link between embryonic and adult neural stem cells was unknown. The current study, Alvarez-Buylla says, reveals the developmental origin of adult neural stem cells and provides a technique for targeting and modifying these cells genetically in mice. “Identifying the lineage of the primary
progenitors in the brain is very basic new information that should help in future attempts to use stem-cell therapy for brain repair”, Alvarez-Buylla adds. Magdalena Götz (GSF-National Research Centre for Environment and Health, Munich, Germany) comments, “The finding that adult neural stem cells originate from radial glia at the border between the dorsal and ventral telencephalon develops the important concept of a continuous lineage relationship between developmental neurogenesis from radial glia and adult neurogenesis from a subset of astrocytes.” Positional specification of the radial glia ancestors may explain why only a few (not most) astrocytes become stem cells; this could be a new approach for endowing astrocytes with stem-cell potential in brain lesions, Götz says.
Kathleen Wildasin http://neurology.thelancet.com Vol 4 February 2005
Olig1 needed for remyelination Researchers in the USA and UK report that the transcription factor Olig1 is needed in the nucleus for the differentiation of oligodendrocytes in adult mice, and therefore for remyelination (Science, 2004; 306: 2111–15). The finding may have an application in the treatment of multiple sclerosis (MS). “Olig1 and a close structural homologue, Olig 2, are both expressed during the development of the nervous system”, explains US group leader Charles Stiles (Dana-Farber Cancer Institute, Boston, MA, USA). “But whereas Olig2 is essential for oligodendrocyte and neuron specification during this period, Olig1 seems not to be—in fact, no-one is sure what it does. Our work shows that Olig1 is certainly needed for any remyelination to occur.” Stiles’ team used antibodies to locate Olig1 and Olig2 during the development and repair of the nervous system
in mice. Olig2 was found in the nuclei of CNS cells at all stages of whitematter development. However, nearly all the Olig1 had moved from the nucleus to the cytoplasm by 2 weeks after birth, the developmental stage at which progenitor cells differentiate into myelin-basic-protein-positive oligodendrocytes. When the UK research group (University of Cambridge) examined mice in which demyelination had been chemically induced, Olig1 was found in the nucleus of cells in early remyelinating lesions, as well as in the remyelinating cerebral lesions in postmortem brain tissue from patients who had MS. These findings suggest that repetition of Olig1’s localisation in the nucleus as seen during development might be needed for repair. Indeed, in repaired tissue, Olig1 was again found in the cytoplasm.
“However, Olig1–/– mice—which undergo largely normal myelination during development—were unable to remyelinate”, explains Stiles. “When [we followed] oligodendrocyte maturation in demyelinated Olig1 knockout mice, the progenitors of these cells were unable to differentiate. So, it seems that although Olig1 is not needed for oligodendrocyte differentiation during development, it is required for remyelination, and it has to be located in the nucleus if the signal to mature is to be understood.” “It’s not yet clear whether there is any failure of the Olig1 system in MS that might hinder remyelination”, remarks Peter Dowling (New Jersey Medical School, East Orange, NJ, USA). “If there is, this might offer new therapeutic targets.”
Adrian Burton
New role for radial glia The recent finding that adult neural stem cells in the subventricular zone are derived from radial glia could have implications for the therapeutic use of stem cells. To test the hypothesis that radial glia in the neonatal brain produce the neurogenic astrocytes found in the adult subventricular zone, Arturo Alvarez-Buylla (Department of Neurological Surgery, University of California, San Francisco, USA) and colleagues traced the progeny of radial glia in newborn mice (Proc Natl Acad Sci USA 2004; 101: 17528–32). “We tagged a subpopulation of radial glia in the neonatal lateral ventricle and showed that these cells produce all of the major brain-cell types, including neurons, astrocytes, and oligodendrocytes”, Alvarez-Buylla told The Lancet Neurology. “More importantly, we showed that neonatal radial glia give rise to the subventricular zone astrocytes that produce neurons 80
throughout life in the adult brain.” Previous research suggested that the brain has two separate lineages: one for neurons and another for glial cells. In the late 1980s, studies in adult birds suggested that radial glia were not involved in the formation of glial cells but were the precursors of neurons, Alvarez-Buylla says. More recent studies report that radial glia in the developing brains of rodents are also stem cells, and cells with glial characteristics have been identified as the primary precursors of new neurons in adult rodents. Although these findings prompted a major conceptual shift in the understanding of cell origin in the brain, the link between embryonic and adult neural stem cells was unknown. The current study, Alvarez-Buylla says, reveals the developmental origin of adult neural stem cells and provides a technique for targeting and modifying these cells genetically in mice. “Identifying the lineage of the primary
progenitors in the brain is very basic new information that should help in future attempts to use stem-cell therapy for brain repair”, Alvarez-Buylla adds. Magdalena Götz (GSF-National Research Centre for Environment and Health, Munich, Germany) comments, “The finding that adult neural stem cells originate from radial glia at the border between the dorsal and ventral telencephalon develops the important concept of a continuous lineage relationship between developmental neurogenesis from radial glia and adult neurogenesis from a subset of astrocytes.” Positional specification of the radial glia ancestors may explain why only a few (not most) astrocytes become stem cells; this could be a new approach for endowing astrocytes with stem-cell potential in brain lesions, Götz says.
Kathleen Wildasin http://neurology.thelancet.com Vol 4 February 2005