The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform
David S Latchman - One of the best experts on this subject based on the ideXlab platform.
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inhibition of neuronal Process Outgrowth and neuronal specific gene activation by the brn 3b transcription factor
Journal of Biological Chemistry, 1997Co-Authors: Martin Smith, Sally J Dawson, David S LatchmanAbstract:The differentiation of the ND7 neuronal cell line to a nondividing phenotype bearing numerous neurite Processes is accompanied by a dramatic increase in the levels of the activating POU family transcription factor Brn-3a and a corresponding fall in the levels of the closely related inhibitory factor Brn-3b. We have previously shown that the artificial overexpression of Brn-3a in these cells can induce neurite Outgrowth and the activation of genes encoding synaptic vesicle proteins in the absence of a differentiation-inducing stimulus. Here we show that overexpression of Brn-3b can reduce Process Outgrowth and synaptic vesicle gene expression following exposure to a stimulus which would normally induce differentiation. These inhibitory effects are abolished by altering a single amino acid in the POU homeodomain of Brn-3b to its equivalent in Brn-3a. The converse mutation in Brn-3a allows it to inhibit Process Outgrowth in response to a differentiation-inducing stimulus. Hence a single amino acid difference results in these closely related factors having opposite effects and allows the balance between them to regulate differentiation.
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the brn 3a transcription factor induces neuronal Process Outgrowth and the coordinate expression of genes encoding synaptic proteins
Molecular and Cellular Biology, 1997Co-Authors: Martin Smith, Sally J Dawson, David S LatchmanAbstract:The Brn-3a POU family transcription factor is expressed only in posmitotic neurons in the central nervous system and identifies the first differentiated neurons to appear in the midbrain, hindbrain, and spinal cord during development. This factor is also induced when undifferentiated proliferating ND7 cells cease dividing and differentiate to a mature neuronal-like phenotype bearing numerous neurite Processes. We show that overexpression of Brn-3a in undifferentiated ND7 cells induces a mature neuronal phenotype characterized by Process Outgrowth and the induction of genes encoding synaptic proteins, although the cells continue to proliferate. In contrast, the closely related factors Brn-3b and Brn-3c do not have this effect. Although the N-terminal activation domain of Brn-3a is required for maximum induction of neurite Outgrowth and gene expression, these effects are primarily dependent on the DNA binding POU domain, which also acts as an activation domain. Overexpression of the isolated POU domain of Brn-3a is sufficient to induce neurite Outgrowth, while the ability of full-length Brn-3a to do so is abolished by mutating a single amino acid in the Brn-3a POU homeodomain to its equivalent in Brn-3b. Thus, Brn-3a appears to play a critical role in the specification of the mature neuronal phenotype, acting by stimulating the expression of genes whose products are required for Process Outgrowth and synapse formation.
Christiane Richterlandsberg - One of the best experts on this subject based on the ideXlab platform.
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dimethylsulfoniopropionate promotes Process Outgrowth in neural cells and exerts protective effects against tropodithietic acid
Marine Drugs, 2016Co-Authors: Heidi Wichmann, Thorsten Brinkhoff, Meinhard Simon, Christiane RichterlandsbergAbstract:The marine environment harbors a plethora of bioactive substances, including drug candidates of potential value in the field of neuroscience. The present study was undertaken to investigate the effects of dimethylsulfoniopropionate (DMSP), produced by several algae, corals and higher plants, on cells of the mammalian nervous system, i.e., neuronal N2a and OLN-93 cells as model system for nerve cells and glia, respectively. Additionally, the protective capabilities of DMSP were assessed in cells treated with tropodithietic acid (TDA), a marine metabolite produced by several Roseobacter clade bacteria. Both cell lines, N2a and OLN-93, have previously been shown to be a sensitive target for the action of TDA, and cytotoxic effects of TDA have been connected to the induction of oxidative stress. Our data shows that DMSP promotes Process Outgrowth and microtubule reorganization and bundling, accompanied by an increase in alpha-tubulin acetylation. Furthermore, DMSP was able to prevent the cytotoxic effects exerted by TDA, including the breakdown of the mitochondrial membrane potential, upregulation of heat shock protein Hsp32 and activation of the extracellular signal-regulated kinases 1/2 (ERK1/2). Our study points to the conclusion that DMSP provides an antioxidant defense, not only in algae but also in mammalian neural cells.
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downregulation of the microtubule associated protein tau impairs Process Outgrowth and myelin basic protein mrna transport in oligodendrocytes
Glia, 2015Co-Authors: Veronika Seiberlich, Nina G Bauer, Lisa Schwarz, Charles Ffrenchconstant, Olaf Goldbaum, Christiane RichterlandsbergAbstract:Oligodendrocytes, the myelin forming cells of the CNS, are characterized by their numerous membranous extensions, which enwrap neuronal axons and form myelin sheaths. During differentiation oligodendrocytes pass different morphological stages, downregulate the expression of the proteoglycan NG2, and acquire major myelin specific proteins, such as myelin basic proteins (MBP) and proteolipid protein. MBP mRNA is transported in RNA granules along the microtubules (MTs) to the periphery and translated locally. MTs participate in the elaboration and stabilization of the myelin forming extensions and are essential for cellular sorting Processes. Their dynamic properties are regulated by microtubule associated proteins (MAPs). The MAP tau is present in oligodendrocytes and involved in the regulation and stabilization of the MT network. To further elucidate the functional significance of tau in oligodendrocytes, we have downregulated tau by siRNA technology and studied the effects on cell differentiation and neuron-glia contact formation. The data show that tau knockdown impairs Process Outgrowth and leads to a decrease in MBP expression. Furthermore, MBP mRNA transport to distant cellular extensions is impaired and cells remain in the NG2 stage. In myelinating cocultures with dorsal root ganglion neurons, oligodendrocyte precursor cells after tau miR RNA lentiviral knockdown develop into NG2 positive cells with very long and thin Processes, contacting axons loosely, but fail to form internodes. This demonstrates that tau is important for MBP mRNA transport and involved in Process formation. The disturbance of the balance of tau leads to abnormalities in oligodendrocyte differentiation, neuron-glia contact formation and the early myelination Process.
Miriam B Goodman - One of the best experts on this subject based on the ideXlab platform.
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the tubulin repertoire of caenorhabditis elegans sensory neurons and its context dependent role in Process Outgrowth
Molecular Biology of the Cell, 2016Co-Authors: Dean Lockhead, Erich M Schwarz, Robert Ohagan, Sebastian Bellotti, Michael Krieg, Maureen M Barr, Alexander R Dunn, Paul W Sternberg, Miriam B GoodmanAbstract:Microtubules contribute to many cellular Processes, including transport, signaling, and chromosome separation during cell division (Kapitein and Hoogenraad, 2015). They are comprised of αβ‐tubulin heterodimers arranged into linear protofilaments and assembled into tubes. Eukaryotes express multiple tubulin isoforms (Gogonea et al., 1999), and there has been a longstanding debate as to whether the isoforms are redundant or perform specialized roles as part of a tubulin code (Fulton and Simpson, 1976). Here, we use the well‐characterized touch receptor neurons (TRNs) of Caenorhabditis elegans to investigate this question, through genetic dissection of Process Outgrowth both in vivo and in vitro. With single‐cell RNA-seq, we compare transcription profiles for TRNs with those of two other sensory neurons, and present evidence that each sensory neuron expresses a distinct palette of tubulin genes. In the TRNs, we analyze Process Outgrowth and show that four tubulins (tba‐1, tba‐2, tbb‐1, and tbb‐2) function partially or fully redundantly, while two others (mec‐7 and mec‐12) perform specialized, context‐dependent roles. Our findings support a model in which sensory neurons express overlapping subsets of tubulin genes whose functional redundancy varies between cell types and in vivo and in vitro contexts.
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the tubulin repertoire of c elegans sensory neurons and its context dependent role in Process Outgrowth
bioRxiv, 2016Co-Authors: Dean Lockhead, Erich M Schwarz, Robert Ohagan, Sebastian Bellotti, Michael Krieg, Maureen M Barr, Alexander R Dunn, Paul W Sternberg, Miriam B GoodmanAbstract:Microtubules contribute to many cellular Processes, including transport, signaling, and chromosome separation during cell division (Kapitein and Hoogenraad, 2015). They are comprised of α-β tubulin heterodimers arranged into linear protofilaments and assembled into tubes. Eukaryotes express multiple tubulin isoforms (Gogonea et al., 1999), and there has been a longstanding debate as to whether the isoforms are redundant or perform specialized roles as part of a tubulin code (Fulton and Simpson, 1976). Here, we use the well characterized touch receptor neurons (TRNs) of Caenorhabditis elegans to investigate this question, through genetic dissection of Process Outgrowth both in vivo and in vitro. With single cell RNA-seq, we compare transcription profiles for TRNs with those of two other sensory neurons, and present evidence that each sensory neuron expresses a distinct palette of tubulin genes. In the TRNs, we analyze Process Outgrowth and show that four tubulins (tba-1, tba-2, tbb-1, and tbb-2) function partially or fully redundantly, while two others (mec-7 and mec-12) perform specialized, context dependent roles. Our findings support a model in which sensory neurons express overlapping subsets of tubulin genes whose functional redundancy varies between cell types and in vivo and in vitro contexts.
Jeremy S H Taylor - One of the best experts on this subject based on the ideXlab platform.
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osteonectin is a schwann cell secreted factor that promotes retinal ganglion cell survival and Process Outgrowth
European Journal of Neuroscience, 2005Co-Authors: Edward T W Bampton, Chi Him, Aviva M Tolkovsky, Jeremy S H TaylorAbstract:We have investigated the factors made by Schwann cells (SCs) that stimulate survival and neurite Outgrowth from postnatal rat retinal ganglion cells (RGCs). These effects are preserved under K252a blockade of the Trk family of neurotrophin receptors and are not fully mimicked by the action of a number of known trophic factors. To identify novel factors responsible for this regenerative activity, we have used a radiolabelling assay. Proteins made by SCs were labelled radioactively and then fed to purified RGCs. The proteins taken up by the RGCs were then isolated and further characterized. Using this assay we have identified a major 40 kDa factor taken up by RGCs, which was microsequenced and shown to be the matricellular protein osteonectin (ON). Using an in vitro assay of purified RGCs we show that ON promotes both survival and neurite Outgrowth. We conclude that ON has a potential new role in promoting CNS repair.
Nina G Bauer - One of the best experts on this subject based on the ideXlab platform.
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downregulation of the microtubule associated protein tau impairs Process Outgrowth and myelin basic protein mrna transport in oligodendrocytes
Glia, 2015Co-Authors: Veronika Seiberlich, Nina G Bauer, Lisa Schwarz, Charles Ffrenchconstant, Olaf Goldbaum, Christiane RichterlandsbergAbstract:Oligodendrocytes, the myelin forming cells of the CNS, are characterized by their numerous membranous extensions, which enwrap neuronal axons and form myelin sheaths. During differentiation oligodendrocytes pass different morphological stages, downregulate the expression of the proteoglycan NG2, and acquire major myelin specific proteins, such as myelin basic proteins (MBP) and proteolipid protein. MBP mRNA is transported in RNA granules along the microtubules (MTs) to the periphery and translated locally. MTs participate in the elaboration and stabilization of the myelin forming extensions and are essential for cellular sorting Processes. Their dynamic properties are regulated by microtubule associated proteins (MAPs). The MAP tau is present in oligodendrocytes and involved in the regulation and stabilization of the MT network. To further elucidate the functional significance of tau in oligodendrocytes, we have downregulated tau by siRNA technology and studied the effects on cell differentiation and neuron-glia contact formation. The data show that tau knockdown impairs Process Outgrowth and leads to a decrease in MBP expression. Furthermore, MBP mRNA transport to distant cellular extensions is impaired and cells remain in the NG2 stage. In myelinating cocultures with dorsal root ganglion neurons, oligodendrocyte precursor cells after tau miR RNA lentiviral knockdown develop into NG2 positive cells with very long and thin Processes, contacting axons loosely, but fail to form internodes. This demonstrates that tau is important for MBP mRNA transport and involved in Process formation. The disturbance of the balance of tau leads to abnormalities in oligodendrocyte differentiation, neuron-glia contact formation and the early myelination Process.