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David H Rowitch - One of the best experts on this subject based on the ideXlab platform.
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Astrocyte Development and heterogeneity
Cold Spring Harbor Perspectives in Biology, 2015Co-Authors: Omer Ali Bayraktar, Luis C Fuentealba, Arturo Alvarezbuylla, David H RowitchAbstract:Astrocytes have many roles within the brain parenchyma, and a subpopulation restricted to germinal niches functions as neural stem cells (NSCs) that produce various types of neuronal progeny in relation to spatiotemporal factors. A growing body of evidence supports the concept of morphological and molecular differences between Astrocytes in different brain regions, which might relate to their derivation from regionally patterned radial glia. Indeed, the notion that Astrocytes are molecularly and functionally heterogeneous could help explain how the central nervous system (CNS) retains embryonic positional information into adulthood. Here, we discuss recent evidence for regionally encoded functions of Astrocytes in the developing and adult CNS to provide an integrated concept of the origin and possible function of Astrocyte heterogeneity. We focus on the regionalization of NSCs in the ventricular-subventricular zone (V-SVZ) of the adult mammalian brain and emerging evidence for a segmental organization of Astrocytes in the developing spinal cord and forebrain. We propose that Astrocytes' diversity will provide fundamental clues to understand regional brain organization and function.
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mechanisms of Astrocyte Development
Patterning and Cell Type Specification in the Developing CNS and PNS#R##N#Comprehensive Developmental Neuroscience, 2013Co-Authors: Anna V. Molofsky, Benjamin Deneen, C Hochstim, David H RowitchAbstract:Abstract Astrocytes are an abundant and essential cell type that play key roles in brain Development and function. However, much remains to be learned about Astrocyte lineage specification and functional maturation during Development. In this chapter, we summarize some of the major findings in Astrocyte biology that have helped to shift the focus from their passive roles as nerve glue to active and critical elements of the developing nervous system. We provide an overview of the current knowledge on Astrocyte specification, lineage, maturation, and diversity. We also address how recent technical advances have shed light on these processes and attempt to reconcile prior knowledge into a more comprehensive understanding of Astrocyte Development.
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specification of Astrocytes by bhlh protein scl in a restricted region of the neural tube
Nature, 2005Co-Authors: David H Rowitch, Yuko Muroyama, Yuko Fujiwara, Stuart H OrkinAbstract:Astrocytes are one of three principal cell types that make up the brain, but surprisingly little is known about how these cells are formed during brain Development. Now a protein called SCL, a basic helix–loop–helix transcription factor, is shown to instruct immature neural stem cells to become Astrocytes. SCL is the first known protein with this role and understanding its function could provide insight into the contributions of Astrocytes in human neurological diseases such as brain cancer, amyotrophic lateral sclerosis and Alzheimer's disease. Astrocytes are the most abundant and functionally diverse glial population in the vertebrate central nervous system (CNS)1. However, the mechanisms underlying Astrocyte specification are poorly understood. It is well established that cellular diversification of neurons in the embryo is generated by position-dependent extrinsic signals and combinatorial interactions of transcription factors that direct specific cell fates by suppressing alternative fates2. It is unknown whether a comparable process determines embryonic Astrocyte identity. Indeed, Astrocyte Development is generally thought to take place in a position-independent manner3,4. Here we show multiple functions of Stem cell leukaemia (Scl, also known as Tal1), which encodes a basic helix–loop–helix (bHLH) transcription factor, in the regulation of both Astrocyte versus oligodendrocyte cell fate acquisition and V2b versus V2a interneuron cell fate acquisition in the p2 domain of the developing vertebrate spinal cord. Our findings demonstrate a regionally restricted transcriptional programme necessary for Astrocyte and V2b interneuron Development, with striking parallels to the involvement of SCL in haematopoiesis. They further indicate that acquisition of embryonic glial subtype identity might be regulated by genetic interactions between SCL and the transcription factor Olig2 in the ventral neural tube.
Valerie A Wallace - One of the best experts on this subject based on the ideXlab platform.
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control of glial precursor cell Development in the mouse optic nerve by sonic hedgehog from retinal ganglion cells
Brain Research, 2008Co-Authors: Gabriel D Dakubo, Shawn Beug, Chantal Mazerolle, Sherry Thurig, Yaping Wang, Valerie A WallaceAbstract:The Development of glial precursor cells in the mammalian optic nerve depends on retinal ganglion cell (RGC) axons, but the signals that mediate this neuron-to-glia interaction have not been fully characterized. Sonic hedgehog (Shh) is expressed by RGCs, and we showed previously that it is required for the specification of Astrocyte lineage cells at the optic disc. To study the role of RGC-derived Shh on Astrocyte Development at later Developmental stages, we generated mice with a conditional ablation of Shh in the peripheral retina and analyzed gene expression and glial cell Development in the optic nerve. Astrocyte Development was initiated in the optic nerves of these mutant mice; however, the expression of Hedgehog (Hh) target genes, Gli1 and Ptch1 and cell cycle genes, Ccnd1 and Cdc25b in the optic nerves were downregulated. Astrocyte proliferation was markedly reduced. Oligodendrocyte precursor cells were fewer in the optic nerves of mutant mice, possibly as a consequence of reduced secretion of growth factors by Astrocytes. At a later Developmental stage, optic nerve axons displayed signs of Wallerian degeneration, including reduction of Astrocyte processes, degenerating glial cells and formation of distended axons. We also demonstrate that the Hh pathway can be activated in optic nerve-derived Astrocytes in vitro, but fails to induce cell cycle gene expression and proliferation. RGC-derived Shh signalling isthus necessary in vivo for maintenance of Astrocyte proliferation, affecting both axo-glial and normal glial cell Development in the optic nerve.
Hirohide Takebayashi - One of the best experts on this subject based on the ideXlab platform.
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Regional- and temporal-dependent changes in the differentiation of Olig2 progenitors in the forebrain, and the impact on Astrocyte Development in the dorsal pallium
Developmental biology, 2008Co-Authors: Katsuhiko Ono, Hirohide Takebayashi, Keisuke Watanabe, Miki Furusho, Kazuyo Ikeda, Takumi Nishizawa, Kazuhiro IkenakaAbstract:Olig2 is a basic helix-loop-helix transcription factor essential for oligodendrocyte and motoneuron Development in the spinal cord. Olig2-positive (Olig2+) cells in the ventricular zone of the ventral telencephalon have been shown to differentiate into GABAergic and cholinergic neurons. However, the fate of Olig2 lineage cells in the postnatal forebrain has not been fully described and Olig2 may regulate the Development of both Astrocytes and oligodendrocytes. Here, we examined the fate of embryonic Olig2+ progenitors using a tamoxifen-inducible Cre/loxP system. Using long-term lineage tracing, Olig2+ cells in the early fetal stage primarily differentiated into GABAergic neurons in the adult telencephalon, while those in later stages gave rise to macroglial cells, both Astrocytes and oligodendrocytes. Olig2+ progenitors in the diencephalon developed into oligodendrocytes, as observed in the spinal cord, and a fraction developed into glutamatergic neurons. Olig2 lineage oligodendrocytes tended to form clusters, probably due to local proliferation at the site of terminal differentiation. In spite of the abundance of Olig2 lineage GABAergic neurons in the normal neocortex, GABAergic neurons seemed to develop at normal density in the Olig2 deficient mouse. Thus, Olig2 is dispensable for GABAergic neuron specification. In contrast, at the late fetal stage in the Olig2 deficient mouse, Astrocyte Development was retarded in the dorsal neocortex, but not in the basal forebrain. Olig2 functions, therefore, in gliogenesis in the dorsal pallium. Short-term lineage tracing experiments revealed that the majority of late Olig2+ cells were not direct descendants of early Olig2+ progenitors in the fetal forebrain. These observations indicate that embryonic Olig2+ progenitor cells change their differentiative properties during Development, and also that Olig2 plays a role in Astrocyte Development in a region-specific manner.
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converse control of oligodendrocyte and Astrocyte lineage Development by sonic hedgehog in the chick spinal cord
Developmental Biology, 2004Co-Authors: Eric Agius, Hirohide Takebayashi, Chadi Soukkarieh, Cathy Danesin, Paulette Kan, Cathy Soula, Philippe CochardAbstract:In the developing spinal cord, oligodendrocyte progenitors (OLPs) originate from the ventral neuroepithelium and the specification of this lineage depends on the inductive activity of Sonic hedgehog (Shh) produced by ventral midline cells. On the other hand, it has been shown that OLP identity is acquired by the coexpression of the transcription factors olig2 and nkx2.2. Although initially expressed in adjacent nonoverlapping domains of the ventral neuroepithelium, these transcription factors become coexpressed in the pMN domain at the time of OLP specification through dorsal extension of the Nkx2.2 domain. Here we show that Shh is sufficient to promote the coexpression of Olig2 and Nkx2.2 in neuroepithelial cells. In addition, Shh activity is necessary for this coexpression since blocking Shh signalling totally abolishes Olig2 expression and impedes dorsal extension of Nkx2.2. Although Shh at these stages affects neuroepithelial cell proliferation, the dorsal extension of the Nkx2.2 domain is not due to progenitor proliferation but to repatterning of the ventral neuroepithelium. Finally, Shh not only stimulates OLP specification but also simultaneously restricts the ventral extension of the Astrocyte progenitor (AP) domain and reduces Astrocyte Development. We propose that specification of distinct glial lineages is the result of a choice that depends on Shh signalling.
Vilma R Martins - One of the best experts on this subject based on the ideXlab platform.
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high levels of cellular prion protein improve Astrocyte Development
FEBS Letters, 2013Co-Authors: Camila Arantes Hartmann, Vilma R Martins, Flavia Regina Souza LimaAbstract:Prion protein (PrPC) has neuroprotective functions and herein we demonstrate that Astrocytes from PrPC-over-expressing mice are more resistant to induced cell death than wild-type Astrocytes. The Stress-Inducible-Protein 1 (STI1), a PrPC ligand, prevents cell death in both wild-type and PrPC-over-expressing Astrocytes through the activation of protein-kinase-A. Cultured embryonic Astrocytes and brain extracts from PrPC-over-expressing mice show higher glial fibrillary acidic protein expression and reduced vimentin and nestin levels when compared to wild-type Astrocytes, suggesting faster Astrocyte maturation in the former mice. Our data indicate that PrPC levels modulate Astrocyte Development, and that PrPC–STI1 interaction contributes to protect against Astrocyte death.
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prion protein and its ligand stress inducible protein 1 regulate Astrocyte Development
Glia, 2009Co-Authors: Camila P Arantes, Flavia Regina Souza Lima, Regina Nomizo, Marilene H Lopes, Glaucia N M Hajj, Vilma R MartinsAbstract:Prion protein (PrPC) interaction with stress inducible protein 1 (STI1) mediates neuronal survival and differentiation. However, the function of PrPC in Astrocytes has not been approached. In this study, we show that STI1 prevents cell death in wild-type Astrocytes in a protein kinase A-dependent manner, whereas PrPC-null Astrocytes were not affected by STI1 treatment. At embryonic day 17, cultured Astrocytes and brain extracts derived from PrPC-null mice showed a reduced expression of glial fibrillary acidic protein (GFAP) and increased vimentin and nestin expression when compared with wild-type, suggesting a slower rate of Astrocyte maturation in PrPC-null animals. Furthermore, PrPC-null Astrocytes treated with STI1 did not differentiate from a flat to a process-bearing morphology, as did wild-type Astrocytes. Remarkably, STI1 inhibited proliferation of both wild-type and PrPC-null Astrocytes in a protein kinase C-dependent manner. Taken together, our data show that PrPC and STI1 are essential to Astrocyte Development and act through distinct signaling pathways. © 2009 Wiley-Liss, Inc.
Flavia Regina Souza Lima - One of the best experts on this subject based on the ideXlab platform.
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high levels of cellular prion protein improve Astrocyte Development
FEBS Letters, 2013Co-Authors: Camila Arantes Hartmann, Vilma R Martins, Flavia Regina Souza LimaAbstract:Prion protein (PrPC) has neuroprotective functions and herein we demonstrate that Astrocytes from PrPC-over-expressing mice are more resistant to induced cell death than wild-type Astrocytes. The Stress-Inducible-Protein 1 (STI1), a PrPC ligand, prevents cell death in both wild-type and PrPC-over-expressing Astrocytes through the activation of protein-kinase-A. Cultured embryonic Astrocytes and brain extracts from PrPC-over-expressing mice show higher glial fibrillary acidic protein expression and reduced vimentin and nestin levels when compared to wild-type Astrocytes, suggesting faster Astrocyte maturation in the former mice. Our data indicate that PrPC levels modulate Astrocyte Development, and that PrPC–STI1 interaction contributes to protect against Astrocyte death.
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prion protein and its ligand stress inducible protein 1 regulate Astrocyte Development
Glia, 2009Co-Authors: Camila P Arantes, Flavia Regina Souza Lima, Regina Nomizo, Marilene H Lopes, Glaucia N M Hajj, Vilma R MartinsAbstract:Prion protein (PrPC) interaction with stress inducible protein 1 (STI1) mediates neuronal survival and differentiation. However, the function of PrPC in Astrocytes has not been approached. In this study, we show that STI1 prevents cell death in wild-type Astrocytes in a protein kinase A-dependent manner, whereas PrPC-null Astrocytes were not affected by STI1 treatment. At embryonic day 17, cultured Astrocytes and brain extracts derived from PrPC-null mice showed a reduced expression of glial fibrillary acidic protein (GFAP) and increased vimentin and nestin expression when compared with wild-type, suggesting a slower rate of Astrocyte maturation in PrPC-null animals. Furthermore, PrPC-null Astrocytes treated with STI1 did not differentiate from a flat to a process-bearing morphology, as did wild-type Astrocytes. Remarkably, STI1 inhibited proliferation of both wild-type and PrPC-null Astrocytes in a protein kinase C-dependent manner. Taken together, our data show that PrPC and STI1 are essential to Astrocyte Development and act through distinct signaling pathways. © 2009 Wiley-Liss, Inc.
