Publications by authors named "Eric S Luth"

16 Publications

  • Page 1 of 1

The Doublesex/Mab-3 domain transcription factor DMD-10 regulates ASH-dependent behavioral responses.

PeerJ 2021 25;9:e10892. Epub 2021 Feb 25.

Biology Department, Suffolk University, Boston, MA, USA.

The Doublesex/Mab-3 Domain transcription factor DMD-10 is expressed in several cell types in , including in the nervous system. We sought to investigate whether DMD-10 is required for normal neuronal function using behavioral assays. We found that mutation of did not broadly affect behavior. mutants were normal in several behavioral assays including a body bends assay for locomotion, egg laying, chemotaxis and response to gentle touch to the body. mutants did have defects in nose-touch responsiveness, which requires the glutamate receptor GLR-1. However, using quantitative fluorescence microscopy to measure levels of a GLR-1::GFP fusion protein in the ventral nerve cord, we found no evidence supporting a difference in the number of GLR-1 synapses or in the amount of GLR-1 present in mutants. mutants did have decreased responsiveness to high osmolarity, which, along with nose-touch, is sensed by the polymodal sensory neuron ASH. Furthermore, mutation of impaired behavioral response to optogenetic activation of ASH, suggesting that promotes neuronal signaling in ASH downstream of sensory receptor activation. Together our results suggest that DMD-10 is important in regulating the frequency of multiple ASH-dependent behavioral responses.
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http://dx.doi.org/10.7717/peerj.10892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916532PMC
February 2021

The WD40-Repeat Protein WDR-20 and the Deubiquitinating Enzyme USP-46 Promote Cell Surface Levels of Glutamate Receptors.

J Neurosci 2021 Apr 23;41(14):3082-3093. Epub 2021 Feb 23.

Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts 02111

Reversible modification of AMPA receptors (AMPARs) with ubiquitin regulates receptor levels at synapses and controls synaptic strength. The conserved deubiquitinating enzyme (DUB) ubiquitin-specific protease-46 (USP-46) removes ubiquitin from AMPARs and protects them from degradation in both and mammals. Although DUBs are critical for diverse physiological processes, the mechanisms that regulate DUBs, especially in the nervous system, are not well understood. We and others previously showed that the WD40-repeat proteins WDR-48 and WDR-20 bind to and stimulate the catalytic activity of USP-46. Here, we identify an activity-dependent mechanism that regulates WDR-20 expression and show that WDR-20 works together with USP-46 and WDR-48 to promote surface levels of the AMPAR GLR-1. , , and loss-of-function mutants exhibit reduced levels of GLR-1 at the neuronal surface and corresponding defects in GLR-1-mediated behavior. Increased expression of WDR-20, but not WDR-48, is sufficient to increase GLR-1 surface levels in an -dependent manner. Loss of , , and function reduces the rate of local GLR-1 insertion in neurites, whereas overexpression of is sufficient to increase the rate of GLR-1 insertion. Genetic manipulations that chronically reduce or increase glutamate signaling result in reciprocal alterations in transcription and homeostatic compensatory changes in surface GLR-1 levels that are dependent on This study identifies as a novel activity-regulated gene that couples chronic changes in synaptic activity with increased local insertion and surface levels of GLR-1 via the DUB USP-46. Deubiquitinating enzymes (DUBs) are critical regulators of synapse development and function; however, the regulatory mechanisms that control their various physiological functions are not well understood. This study identifies a novel role for the DUB ubiquitin-specific protease-46 (USP-46) and its associated regulatory protein WD40-repeat protein-20 (WDR-20) in regulating local insertion of glutamate receptors into the neuronal cell surface. This work also identifies WDR-20 as an activity-regulated gene that couples chronic changes in synaptic activity with homeostatic compensatory increases in surface levels of GLR-1 via USP-46. Given that 35% of USP family DUBs associate with WDR proteins, understanding the mechanisms by which WDR proteins regulate USP-46 could have implications for a large number of DUBs in other cell types.
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http://dx.doi.org/10.1523/JNEUROSCI.1074-20.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026351PMC
April 2021

VER/VEGF receptors regulate AMPA receptor surface levels and glutamatergic behavior.

PLoS Genet 2021 Feb 9;17(2):e1009375. Epub 2021 Feb 9.

Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.

Several intracellular trafficking pathways contribute to the regulation of AMPA receptor (AMPAR) levels at synapses and the control of synaptic strength. While much has been learned about these intracellular trafficking pathways, a major challenge is to understand how extracellular factors, such as growth factors, neuropeptides and hormones, impinge on specific AMPAR trafficking pathways to alter synaptic function and behavior. Here, we identify the secreted ligand PVF-1 and its cognate VEGF receptor homologs, VER-1 and VER-4, as regulators of glutamate signaling in C. elegans. Loss of function mutations in ver-1, ver-4, or pvf-1, result in decreased cell surface levels of the AMPAR GLR-1 and defects in glutamatergic behavior. Rescue experiments indicate that PVF-1 is expressed and released from muscle, whereas the VERs function in GLR-1-expressing neurons to regulate surface levels of GLR-1 and glutamatergic behavior. Additionally, ver-4 is unable to rescue glutamatergic behavior in the absence of pvf-1, suggesting that VER function requires endogenous PVF-1. Inducible expression of a pvf-1 rescuing transgene suggests that PVF-1 can function in the mature nervous system to regulate GLR-1 signaling. Genetic double mutant analysis suggests that the VERs act together with the VPS-35/retromer recycling complex to promote cell surface levels of GLR-1. Our data support a genetic model whereby PVF-1/VER signaling acts with retromer to promote recycling and cell surface levels of GLR-1 to control behavior.
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http://dx.doi.org/10.1371/journal.pgen.1009375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899335PMC
February 2021

The Snail transcription factor CES-1 regulates glutamatergic behavior in C. elegans.

PLoS One 2021 2;16(2):e0245587. Epub 2021 Feb 2.

Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.

Regulation of AMPA-type glutamate receptor (AMPAR) expression and function alters synaptic strength and is a major mechanism underlying synaptic plasticity. Although transcription is required for some forms of synaptic plasticity, the transcription factors that regulate AMPA receptor expression and signaling are incompletely understood. Here, we identify the Snail family transcription factor ces-1 in an RNAi screen for conserved transcription factors that regulate glutamatergic behavior in C. elegans. ces-1 was originally discovered as a selective cell death regulator of neuro-secretory motor neuron (NSM) and I2 interneuron sister cells in C. elegans, and has almost exclusively been studied in the NSM cell lineage. We found that ces-1 loss-of-function mutants have defects in two glutamatergic behaviors dependent on the C. elegans AMPA receptor GLR-1, the mechanosensory nose-touch response and spontaneous locomotion reversals. In contrast, ces-1 gain-of-function mutants exhibit increased spontaneous reversals, and these are dependent on glr-1 consistent with these genes acting in the same pathway. ces-1 mutants have wild type cholinergic neuromuscular junction function, suggesting that they do not have a general defect in synaptic transmission or muscle function. The effect of ces-1 mutation on glutamatergic behaviors is not due to ectopic cell death of ASH sensory neurons or GLR-1-expressing neurons that mediate one or both of these behaviors, nor due to an indirect effect on NSM sister cell deaths. Rescue experiments suggest that ces-1 may act, in part, in GLR-1-expressing neurons to regulate glutamatergic behaviors. Interestingly, ces-1 mutants suppress the increased reversal frequencies stimulated by a constitutively-active form of GLR-1. However, expression of glr-1 mRNA or GFP-tagged GLR-1 was not decreased in ces-1 mutants suggesting that ces-1 likely promotes GLR-1 function. This study identifies a novel role for ces-1 in regulating glutamatergic behavior that appears to be independent of its canonical role in regulating cell death in the NSM cell lineage.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245587PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853468PMC
February 2021

Measuring Mitochondrial Dysfunction Caused by Soluble α-Synuclein Oligomers.

Methods Mol Biol 2019 ;1948:183-198

Department of Neurology, Columbia University Medical Center, New York, NY, USA.

Accumulation of misfolded αSyn and mitochondrial dysfunction are central features of Parkinson's disease. Growing evidence points to a relationship between these two phenomena as oligomeric α-synuclein (αSyn) can interact with mitochondria and impair their function. Standardization of methods to prepare αSyn oligomers and isolate functional mitochondria will facilitate efforts to expand upon early findings. Here we present detailed protocols for preparing soluble αSyn oligomers; for isolating functional mitochondria from mouse tissue; and for simultaneously measuring several aspects of mitochondrial physiology. These protocols will benefit future studies aimed at characterizing the mitotoxicity of αSyn species isolated from the brains of synucleinopathy patients as well as efforts to identify small molecules and genetic or environmental alterations that prevent αSyn-induced mitochondrial dysfunction.
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http://dx.doi.org/10.1007/978-1-4939-9124-2_14DOI Listing
July 2019

Parkinson-causing α-synuclein missense mutations shift native tetramers to monomers as a mechanism for disease initiation.

Nat Commun 2015 Jun 16;6:7314. Epub 2015 Jun 16.

Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

β-Sheet-rich α-synuclein (αS) aggregates characterize Parkinson's disease (PD). αS was long believed to be a natively unfolded monomer, but recent work suggests it also occurs in α-helix-rich tetramers. Crosslinking traps principally tetrameric αS in intact normal neurons, but not after cell lysis, suggesting a dynamic equilibrium. Here we show that freshly biopsied normal human brain contains abundant αS tetramers. The PD-causing mutation A53T decreases tetramers in mouse brain. Neurons derived from an A53T patient have decreased tetramers. Neurons expressing E46K do also, and adding 1-2 E46K-like mutations into the canonical αS repeat motifs (KTKEGV) further reduces tetramers, decreases αS solubility and induces neurotoxicity and round inclusions. The other three fPD missense mutations likewise decrease tetramer:monomer ratios. The destabilization of physiological tetramers by PD-causing missense mutations and the neurotoxicity and inclusions induced by markedly decreasing tetramers suggest that decreased α-helical tetramers and increased unfolded monomers initiate pathogenesis. Tetramer-stabilizing compounds should prevent this.
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http://dx.doi.org/10.1038/ncomms8314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490410PMC
June 2015

The AP2 clathrin adaptor protein complex regulates the abundance of GLR-1 glutamate receptors in the ventral nerve cord of Caenorhabditis elegans.

Mol Biol Cell 2015 May 18;26(10):1887-900. Epub 2015 Mar 18.

Department of Developmental, Molecular & Chemical Biology

Regulation of glutamate receptor (GluR) abundance at synapses by clathrin-mediated endocytosis can control synaptic strength and plasticity. We take advantage of viable, null mutations in subunits of the clathrin adaptor protein 2 (AP2) complex in Caenorhabditis elegans to characterize the in vivo role of AP2 in GluR trafficking. In contrast to our predictions for an endocytic adaptor, we found that levels of the GluR GLR-1 are decreased at synapses in the ventral nerve cord (VNC) of animals with mutations in the AP2 subunits APM-2/μ2, APA-2/α, or APS-2/σ2. Rescue experiments indicate that APM-2/μ2 functions in glr-1-expressing interneurons and the mature nervous system to promote GLR-1 levels in the VNC. Genetic analyses suggest that APM-2/μ2 acts upstream of GLR-1 endocytosis in the VNC. Consistent with this, GLR-1 accumulates in cell bodies of apm-2 mutants. However, GLR-1 does not appear to accumulate at the plasma membrane of the cell body as expected, but instead accumulates in intracellular compartments including Syntaxin-13- and RAB-14-labeled endosomes. This study reveals a novel role for the AP2 clathrin adaptor in promoting the abundance of GluRs at synapses in vivo, and implicates AP2 in the regulation of GluR trafficking at an early step in the secretory pathway.
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http://dx.doi.org/10.1091/mbc.E14-06-1048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436833PMC
May 2015

Purification of α-synuclein from human brain reveals an instability of endogenous multimers as the protein approaches purity.

Biochemistry 2015 Jan 23;54(2):279-92. Epub 2014 Dec 23.

Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts 02115, United States.

Despite two decades of research, the structure-function relationships of endogenous, physiological forms of α-synuclein (αSyn) are not well understood. Most in vitro studies of this Parkinson's disease-related protein have focused on recombinant αSyn that is unfolded and monomeric, assuming that this represents its state in the normal human brain. Recently, we have provided evidence that αSyn exists in considerable part in neurons, erythrocytes, and other cells as a metastable multimer that principally sizes as a tetramer. In contrast to recombinant αSyn, physiological tetramers purified from human erythrocytes have substantial α-helical content and resist pathological aggregation into β-sheet rich fibers. Here, we report the first method to fully purify soluble αSyn from the most relevant source, human brain. We describe protocols that purify αSyn to homogeneity from nondiseased human cortex using ammonium sulfate precipitation, gel filtration, and ion exchange, hydrophobic interaction, and affinity chromatographies. Cross-linking of the starting material and the partially purified chromatographic fractions revealed abundant αSyn multimers, including apparent tetramers, but these were destabilized in large part to monomers during the final purification step. The method also fully purified the homologue β-synuclein, with a similar outcome. Circular dichroism spectroscopy showed that purified, brain-derived αSyn can display more helical content than the recombinant protein, but this result varied. Collectively, our data suggest that purifying αSyn to homogeneity destabilizes native, α-helix-rich multimers that exist in intact and partially purified brain samples. This finding suggests existence of a stabilizing cofactor (e.g., a small lipid) present inside neurons that is lost during final purification.
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http://dx.doi.org/10.1021/bi501188aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303315PMC
January 2015

N-alpha-acetylation of α-synuclein increases its helical folding propensity, GM1 binding specificity and resistance to aggregation.

PLoS One 2014 30;9(7):e103727. Epub 2014 Jul 30.

Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.

A switch in the conformational properties of α-synuclein (αS) is hypothesized to be a key step in the pathogenic mechanism of Parkinson's disease (PD). Whereas the beta-sheet-rich state of αS has long been associated with its pathological aggregation in PD, a partially alpha-helical state was found to be related to physiological lipid binding; this suggests a potential role of the alpha-helical state in controlling synaptic vesicle cycling and resistance to β-sheet rich aggregation. N-terminal acetylation is the predominant post-translational modification of mammalian αS. Using circular dichroism, isothermal titration calorimetry, and fluorescence spectroscopy, we have analyzed the effects of N-terminal acetylation on the propensity of recombinant human αS to form the two conformational states in interaction with lipid membranes. Small unilamellar vesicles of negatively charged lipids served as model membranes. Consistent with previous NMR studies using phosphatidylserine, we found that membrane-induced α-helical folding was enhanced by N-terminal acetylation and that greater exothermic heat could be measured upon vesicle binding of the modified protein. Interestingly, the folding and lipid binding enhancements with phosphatidylserine in vitro were weak when compared to that of αS with GM1, a lipid enriched in presynaptic membranes. The resultant increase in helical folding propensity of N-acetylated αS enhanced its resistance to aggregation. Our findings demonstrate the significance of the extreme N-terminus for folding nucleation, for relative GM1 specificity of αS-membrane interaction, and for a protective function of N-terminal-acetylation against αS aggregation mediated by GM1.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0103727PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116227PMC
November 2015

Soluble, prefibrillar α-synuclein oligomers promote complex I-dependent, Ca2+-induced mitochondrial dysfunction.

J Biol Chem 2014 Aug 18;289(31):21490-507. Epub 2014 Jun 18.

From the Center for Neurologic Diseases, Department of Neurology, and

α-Synuclein (αSyn) aggregation and mitochondrial dysfunction both contribute to the pathogenesis of Parkinson disease (PD). Although recent studies have suggested that mitochondrial association of αSyn may disrupt mitochondrial function, it is unclear what aggregation state of αSyn is most damaging to mitochondria and what conditions promote or inhibit the effect of toxic αSyn species. Because the neuronal populations most vulnerable in PD are characterized by large cytosolic Ca(2+) oscillations that burden mitochondria, we examined mitochondrial Ca(2+) stress in an in vitro system comprising isolated mitochondria and purified recombinant human αSyn in various aggregation states. Using fluorimetry to simultaneously measure four mitochondrial parameters, we observed that soluble, prefibrillar αSyn oligomers, but not monomeric or fibrillar αSyn, decreased the retention time of exogenously added Ca(2+), promoted Ca(2+)-induced mitochondrial swelling and depolarization, and accelerated cytochrome c release. Inhibition of the permeability transition pore rescued these αSyn-induced changes in mitochondrial parameters. Interestingly, the mitotoxic effects of αSyn were specifically dependent upon both electron flow through complex I and mitochondrial uptake of exogenous Ca(2+). Our results suggest that soluble prefibrillar αSyn oligomers recapitulate several mitochondrial phenotypes previously observed in animal and cell models of PD: complex I dysfunction, altered membrane potential, disrupted Ca(2+) homeostasis, and enhanced cytochrome c release. These data reveal how the association of oligomeric αSyn with mitochondria can be detrimental to the function of cells with high Ca(2+)-handling requirements.
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http://dx.doi.org/10.1074/jbc.M113.545749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4118111PMC
August 2014

In vivo cross-linking reveals principally oligomeric forms of α-synuclein and β-synuclein in neurons and non-neural cells.

J Biol Chem 2013 Mar 14;288(9):6371-85. Epub 2013 Jan 14.

Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

Aggregation of α-synuclein (αSyn) in neurons produces the hallmark cytopathology of Parkinson disease and related synucleinopathies. Since its discovery, αSyn has been thought to exist normally in cells as an unfolded monomer. We recently reported that αSyn can instead exist in cells as a helically folded tetramer that resists aggregation and binds lipid vesicles more avidly than unfolded recombinant monomers (Bartels, T., Choi, J. G., and Selkoe, D. J. (2011) Nature 477, 107-110). However, a subsequent study again concluded that cellular αSyn is an unfolded monomer (Fauvet, B., Mbefo, M. K., Fares, M. B., Desobry, C., Michael, S., Ardah, M. T., Tsika, E., Coune, P., Prudent, M., Lion, N., Eliezer, D., Moore, D. J., Schneider, B., Aebischer, P., El-Agnaf, O. M., Masliah, E., and Lashuel, H. A. (2012) J. Biol. Chem. 287, 15345-15364). Here we describe a simple in vivo cross-linking method that reveals a major ~60-kDa form of endogenous αSyn (monomer, 14.5 kDa) in intact cells and smaller amounts of ~80- and ~100-kDa forms with the same isoelectric point as the 60-kDa species. Controls indicate that the apparent 60-kDa tetramer exists normally and does not arise from pathological aggregation. The pattern of a major 60-kDa and minor 80- and 100-kDa species plus variable amounts of free monomers occurs endogenously in primary neurons and erythroid cells as well as neuroblastoma cells overexpressing αSyn. A similar pattern occurs for the homologue, β-synuclein, which does not undergo pathogenic aggregation. Cell lysis destabilizes the apparent 60-kDa tetramer, leaving mostly free monomers and some 80-kDa oligomer. However, lysis at high protein concentrations allows partial recovery of the 60-kDa tetramer. Together with our prior findings, these data suggest that endogenous αSyn exists principally as a 60-kDa tetramer in living cells but is lysis-sensitive, making the study of natural αSyn challenging outside of intact cells.
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http://dx.doi.org/10.1074/jbc.M112.403311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585072PMC
March 2013

β4 integrin marks interstitial myogenic progenitor cells in adult murine skeletal muscle.

J Histochem Cytochem 2012 Jan;60(1):31-44

Program in Genomics, Division of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

Skeletal muscle growth and its regeneration following injury rely on myogenic progenitor cells, a heterogeneous population that includes the satellite cells and other interstitial progenitors. The present study demonstrates that surface expression of β4 integrin marks a population of vessel-associated interstitial muscle progenitor cells. Muscle β4 integrin-positive cells do not express myogenic markers upon isolation. However, they are capable of undergoing myogenic specification in vitro and in vivo: β4 integrin cells differentiate into multinucleated myotubes in culture dishes and contribute to muscle regeneration upon delivery into diseased mice. Subfractionation of β4 integrin-expressing cells based on CD31 expression does not further enrich for myogenic precursors. These findings support the expression of β4 integrin in interstitial, vessel-associated cells with myogenic activity within adult skeletal muscle.
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http://dx.doi.org/10.1369/0022155411428991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283133PMC
January 2012

Biochemical and functional interaction of disrupted-in-schizophrenia 1 and amyloid precursor protein regulates neuronal migration during mammalian cortical development.

J Neurosci 2010 Aug;30(31):10431-40

Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

Although clinically distinct, schizophrenia and Alzheimer's disease are common and devastating disorders that profoundly impair cognitive function. For Alzheimer's disease, key mechanistic insights have emerged from genetic studies that identified causative mutations in amyloid precursor protein (APP) and presenilin. Several genes have been associated with schizophrenia and other major psychoses, and understanding their normal functions will help elucidate the underlying causes of these disorders. One such gene is disrupted-in-schizophrenia 1 (DISC1). DISC1 and APP have been implicated separately in cortical development, with each having roles in both neuronal migration and neurite outgrowth. Here, we report a previously unrecognized biochemical and functional interaction between DISC1 and APP. Using in utero electroporation in the living rat brain, we show that DISC1 acts downstream of APP and Disabled-1 to regulate cortical precursor cell migration. Specifically, overexpression of DISC1 rescues the migration defect caused by a loss of APP expression. Moreover, knockdown of APP in cultured embryonic neurons results in altered subcellular localization of DISC1. Using transfected cells and normal brain tissue, we show that APP and DISC1 coimmunoprecipitate and that the intracellular domain of APP interacts with the N-terminal domain of DISC1. Based on these findings, we hypothesize that the APP cytoplasmic region transiently interacts with DISC1 to help regulate the translocation of DISC1 to the centrosome, where it plays a key role in controlling neuronal migration during cortical development.
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http://dx.doi.org/10.1523/JNEUROSCI.1445-10.2010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018837PMC
August 2010

Bone marrow side population cells are enriched for progenitors capable of myogenic differentiation.

J Cell Sci 2008 May 8;121(Pt 9):1426-34. Epub 2008 Apr 8.

Program in Genomics, Division of Genetics, Children's Hospital Boston, Boston, MA 02115, USA.

Although the contribution of bone marrow-derived cells to regenerating skeletal muscle has been repeatedly documented, there remains considerable debate as to whether this incorporation is exclusively a result of inflammatory cell fusion to regenerating myofibers or whether certain populations of bone marrow-derived cells have the capacity to differentiate into muscle. The present study uses a dual-marker approach in which GFP(+) cells were intravenously transplanted into lethally irradiated beta-galactosidase(+) recipients to allow for simple determination of donor and host contribution to the muscle. FACS analysis of cardiotoxin-damaged muscle revealed that CD45(+) bone-marrow side-population (SP) cells, a group enriched in hematopoietic stem cells, can give rise to CD45(-)/Sca-1(+)/desmin(+) cells capable of myogenic differentiation. Moreover, after immunohistochemical examination of the muscles of both SP- and whole bone marrow-transplanted animals, we noted the presence of myofibers composed only of bone marrow-derived cells. Our findings suggest that a subpopulation of bone marrow SP cells contains precursor cells whose progeny have the potential to differentiate towards a muscle lineage and are capable of de novo myogenesis following transplantation and initiation of muscle repair via chemical damage.
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http://dx.doi.org/10.1242/jcs.021675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437547PMC
May 2008

Co-detection of GFP and dystrophin in skeletal muscle tissue sections.

Biotechniques 2007 Jun;42(6):699-700

Howard Hughes Medical Institute, Chevy Chase, MD, USA.

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http://dx.doi.org/10.2144/000112494DOI Listing
June 2007