Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 13 de 13
Filtrar
1.
J Neurosci ; 33(6): 2432-42, 2013 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-23392672

RESUMO

Oligodendrocyte precursor cells (OPCs) are the major source of myelinating oligodendrocytes during development. These progenitors are highly abundant at birth and persist in the adult where they are distributed throughout the brain. The large abundance of OPCs after completion of myelination challenges their unique role as progenitors in the healthy adult brain. Here we show that adult OPCs of the barrel cortex sense fine extracellular K(+) increases generated by neuronal activity, a property commonly assigned to differentiated astrocytes rather than to progenitors. Biophysical, pharmacological, and single-cell RT-PCR analyses demonstrate that this ability of OPCs establishes itself progressively through the postnatal upregulation of Kir4.1 K(+) channels. In animals with advanced cortical myelination, extracellular stimulation of layer V axons induces slow K(+) currents in OPCs, which amplitude correlates with presynaptic action potential rate. Moreover, using paired recordings, we demonstrate that the discharge of a single neuron can be detected by nearby adult OPCs, indicating that these cells are strategically located to detect local changes in extracellular K(+) concentration during physiological neuronal activity. These results identify a novel unitary neuron-OPC connection, which transmission does not rely on neurotransmitter release and appears late in development. Beyond their abundance in the mature brain, the postnatal emergence of a physiological response of OPCs to neuronal network activity supports the view that in the adult these cells are not progenitors only.


Assuntos
Córtex Cerebral/metabolismo , Células-Tronco Neurais/metabolismo , Oligodendroglia/metabolismo , Potássio/metabolismo , Animais , Animais Recém-Nascidos , Córtex Cerebral/crescimento & desenvolvimento , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Canais de Potássio Corretores do Fluxo de Internalização/biossíntese
2.
Nat Commun ; 15(1): 3016, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589367

RESUMO

Myelodysplastic syndromes (MDS) with mutated SF3B1 gene present features including a favourable outcome distinct from MDS with mutations in other splicing factor genes SRSF2 or U2AF1. Molecular bases of these divergences are poorly understood. Here we find that SF3B1-mutated MDS show reduced R-loop formation predominating in gene bodies associated with intron retention reduction, not found in U2AF1- or SRSF2-mutated MDS. Compared to erythroblasts from SRSF2- or U2AF1-mutated patients, SF3B1-mutated erythroblasts exhibit augmented DNA synthesis, accelerated replication forks, and single-stranded DNA exposure upon differentiation. Importantly, histone deacetylase inhibition using vorinostat restores R-loop formation, slows down DNA replication forks and improves SF3B1-mutated erythroblast differentiation. In conclusion, loss of R-loops with associated DNA replication stress represents a hallmark of SF3B1-mutated MDS ineffective erythropoiesis, which could be used as a therapeutic target.


Assuntos
Síndromes Mielodisplásicas , Estruturas R-Loop , Humanos , Fator de Processamento U2AF/genética , Fatores de Processamento de Serina-Arginina/genética , Fatores de Processamento de RNA/genética , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Mutação , Fatores de Transcrição/genética , Fosfoproteínas/genética
3.
Glia ; 61(8): 1306-19, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23828736

RESUMO

Within the central nervous system, functions of the ATP-gated receptor-channel P2X4 (P2X4R) are still poorly understood, yet P2X4R activation in neurons and microglia coincides with high or pathological neuronal activities. In this study, we investigated the potential involvement of P2X4R in microglial functions in a model of kainate (KA)-induced status epilepticus (SE). We found that SE was associated with an induction of P2X4R expression in the hippocampus, mostly localized in activated microglial cells. In P2X4R-deficient mice, behavioral responses during KA-induced SE were unaltered. However, 48h post SE specific features of microglial activation, such as cell recruitment and upregulation of voltage-dependent potassium channels were impaired in P2X4R-deficient mice, whereas the expression and function of other microglial purinergic receptors remained unaffected. Consistent with the role of P2X4R in activity-dependent degenerative processes, the CA1 area was partially protected from SE-induced neuronal death in P2X4R-deficient mice compared with wild-type animals. Our findings demonstrate that P2X4Rs are brought into play during neuronal hyperexcitability and that they control specific aspects of microglial activation. Our results also suggest that P2X4Rs contribute to excitotoxic damages by regulating microglial activation.


Assuntos
Hipocampo/metabolismo , Microglia/metabolismo , Receptores Purinérgicos P2X4/fisiologia , Estado Epiléptico/metabolismo , Animais , Proliferação de Células , Hipocampo/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/patologia , Técnicas de Cultura de Órgãos , Receptores Purinérgicos P2X4/biossíntese , Receptores Purinérgicos P2X4/deficiência , Estado Epiléptico/patologia , Regulação para Cima/fisiologia
4.
Blood Adv ; 7(13): 3265-3275, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-36930820

RESUMO

Transcription factor Forkhead box P1 (FOXP1) belongs to the same protein family as the FOXOs that are well-known regulators of murine hematopoietic stem progenitor cell (HSPC) maintenance via dampening oxidative stress. FOXP1 and FOXOs can play opposite, or similar, roles depending on cell context; they can crossregulate each other's expression. In a previous study, we have shown that FOXP1 contributes to healthy human HSPC and acute myeloid leukemia (AML) cell growth. Here, we investigated the role of FOXP1 in HSPCs and AML cell oxidative stress defense in a human context. FOXP1 expression level was associated with an inferior survival outcome in patients with cytogenetically normal AML. FOXP1 knockdown enhanced superoxide anion levels of human-committed CD34+CD38+ cells but not stem cell-enriched CD34+CD38- HSPCs or AML cells in vitro. FOXP1 knockdown triggered enhanced NRF2 activity and increased cell oxidative stress. FOXP1 had no impact on FOXO1/3/4 expression in these cells; genetic and pharmacological inhibition of FOXOs did not change superoxide anion levels of human HSPCs or AML cells. Moreover, FOXP1 antioxidant activity was independent of changes in expression of superoxide dismutase 1 and 2 or catalase. Instead, FOXP1 upregulated expression of the stress sensor SIRT1 by stabilizing SIRT1 protein. FOXP1 loss sensitized AML cells to chemotherapy. Together, this study identified FOXP1 as a new safeguard against myeloid progenitor oxidative stress, which works independently of FOXOs but through SIRT1 and contributes to AML chemoresistance. It proposes FOXP1 expression/activity as a promising target to overcome drug resistance of AML HSPCs.


Assuntos
Leucemia Mieloide Aguda , Sirtuína 1 , Humanos , Animais , Camundongos , Sirtuína 1/genética , Sirtuína 1/metabolismo , Superóxidos/metabolismo , Leucemia Mieloide Aguda/genética , Células-Tronco Hematopoéticas/metabolismo , Estresse Oxidativo , Proteínas Repressoras/genética , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo
5.
Mol Metab ; 43: 101108, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33137488

RESUMO

OBJECTIVE: Glucose production in the blood requires the expression of glucose-6 phosphatase (G6Pase), a key enzyme that allows glucose-6 phosphate (G6P) hydrolysis into free glucose and inorganic phosphate. We previously reported that the hepatic suppression of G6Pase leads to G6P accumulation and to metabolic reprogramming in hepatocytes from liver G6Pase-deficient mice (L.G6pc-/-). Interestingly, the activity of the transcription factor carbohydrate response element-binding protein (ChREBP), central for de novo lipid synthesis, is markedly activated in L.G6pc-/- mice, which consequently rapidly develop NAFLD-like pathology. In the current work, we assessed whether a selective deletion of ChREBP could prevent hepatic lipid accumulation and NAFLD initiation in L.G6pc-/- mice. METHODS: We generated liver-specific ChREBP (L.Chrebp-/-)- and/or G6Pase (L.G6pc-/-)-deficient mice using a Cre-lox strategy in B6.SACreERT2 mice. Mice were fed a standard chow diet or a high-fat diet for 10 days. Markers of hepatic metabolism and cellular stress were analysed in the liver of control, L. G6pc-/-, L. Chrebp-/- and double knockout (i.e., L.G6pc-/-.Chrebp-/-) mice. RESULTS: We observed that there was a dramatic decrease in lipid accumulation in the liver of L.G6pc-/-.Chrebp-/- mice. At the mechanistic level, elevated G6P concentrations caused by lack of G6Pase are rerouted towards glycogen synthesis. Importantly, this exacerbated glycogen accumulation, leading to hepatic water retention and aggravated hepatomegaly. This caused animal distress and hepatocyte damage, characterised by ballooning and moderate fibrosis, paralleled with acute endoplasmic reticulum stress. CONCLUSIONS: Our study reveals the crucial role of the ChREBP-G6Pase duo in the regulation of G6P-regulated pathways in the liver.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Metabolismo dos Lipídeos/fisiologia , Monoéster Fosfórico Hidrolases/metabolismo , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Glucose/metabolismo , Glucose-6-Fosfatase/metabolismo , Glucose-6-Fosfato/metabolismo , Hepatócitos/metabolismo , Hidrólise , Lipídeos/fisiologia , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Monoéster Fosfórico Hidrolases/genética
6.
Arthritis Rheumatol ; 73(11): 1976-1985, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33881229

RESUMO

OBJECTIVE: The clinical relevance of antiphospholipid antibodies (aPLs) in COVID-19 is controversial. This study was undertaken to investigate the prevalence and prognostic value of conventional and nonconventional aPLs in patients with COVID-19. METHODS: This was a multicenter, prospective observational study in a French cohort of patients hospitalized with suspected COVID-19. RESULTS: Two hundred forty-nine patients were hospitalized with suspected COVID-19, in whom COVID-19 was confirmed in 154 and not confirmed in 95. We found a significant increase in lupus anticoagulant (LAC) positivity among patients with COVID-19 compared to patients without COVID-19 (60.9% versus 23.7%; P < 0.001), while prevalence of conventional aPLs (IgG and IgM anti-ß2 -glycoprotein I and IgG and IgM anticardiolipin isotypes) and nonconventional aPLs (IgA isotype of anticardiolipin, IgA isotype of anti-ß2 -glycoprotein I, IgG and IgM isotypes of anti-phosphatidylserine/prothrombin, and IgG and IgM isotypes of antiprothrombin) was low in both groups. Patients with COVID-19 who were positive for LAC, as compared to patients with COVID-19 who were negative for LAC, had higher levels of fibrinogen (median 6.0 gm/liter [interquartile range 5.0-7.0] versus 5.3 gm/liter [interquartile range 4.3-6.4]; P = 0.028) and C-reactive protein (CRP) (median 115.5 mg/liter [interquartile range 66.0-204.8] versus 91.8 mg/liter [interquartile range 27.0-155.1]; P = 0.019). Univariate analysis did not show any association between LAC positivity and higher risks of venous thromboembolism (VTE) (odds ratio 1.02 [95% confidence interval 0.44-2.43], P = 0.95) or in-hospital mortality (odds ratio 1.80 [95% confidence interval 0.70-5.05], P = 0.24). With and without adjustment for CRP level, age, and sex, Kaplan-Meier survival curves according to LAC positivity confirmed the absence of an association with VTE or in-hospital mortality (unadjusted P = 0.64 and P = 0.26, respectively; adjusted hazard ratio 1.13 [95% confidence interval 0.48-2.60] and 1.80 [95% confidence interval 0.67-5.01], respectively). CONCLUSION: Patients with COVID-19 have an increased prevalence of LAC positivity associated with biologic markers of inflammation. However, LAC positivity at the time of hospital admission is not associated with VTE risk and/or in-hospital mortality.


Assuntos
COVID-19/complicações , Inibidor de Coagulação do Lúpus/sangue , Tromboembolia Venosa/etiologia , Idoso , Idoso de 80 Anos ou mais , COVID-19/sangue , COVID-19/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida , Tromboembolia Venosa/sangue
7.
J Thromb Haemost ; 19(7): 1823-1830, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33830623

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with vascular inflammation and endothelial injury. OBJECTIVES: To correlate circulating angiogenic markers vascular endothelial growth factor A (VEGF-A), placental growth factor (PlGF), and fibroblast growth factor 2 (FGF-2) to in-hospital mortality in COVID-19 adult patients. METHODS: Consecutive ambulatory and hospitalized patients with COVID-19 infection were enrolled. VEGF-A, PlGF, and FGF-2 were measured in each patient ≤48 h following admission. RESULTS: The study enrolled 237 patients with suspected COVID-19: 208 patients had a positive diagnostic for COVID-19, of whom 23 were mild outpatients and 185 patients hospitalized after admission. Levels of VEGF-A, PlGF, and FGF-2 significantly increase with the severity of the disease (P < .001). Using a logistic regression model, we found a significant association between the increase of FGF-2 or PlGF and mortality (odds ratio [OR] 1.11, 95% confidence interval [CI; 1.07-1.16], P < .001 for FGF-2 and OR 1.07 95% CI [1.04-1.10], P < .001 for PlGF) while no association were found for VEGF-A levels. Receiver operating characteristic curve analysis was performed and we identified PlGF above 30 pg/ml as the best predictor of in-hospital mortality in COVID-19 patients. Survival analysis for PlGF confirmed its interest for in-hospital mortality prediction, by using a Kaplan-Meier survival curve (P = .001) and a Cox proportional hazard model adjusted to age, body mass index, D-dimer, and C-reactive protein (3.23 95% CI [1.29-8.11], P = .001). CONCLUSION: Angiogenic factor PlGF is a relevant predictive factor for in-hospital mortality in COVID-19 patients. More than a biomarker, we hypothesize that PlGF blocking strategies could be a new interesting therapeutic approach in COVID-19.


Assuntos
COVID-19 , Fator A de Crescimento do Endotélio Vascular , Adulto , Biomarcadores , Feminino , Mortalidade Hospitalar , Humanos , Fator de Crescimento Placentário , SARS-CoV-2
8.
Cell Death Dis ; 12(3): 258, 2021 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-33707411

RESUMO

The circulating metabolome provides a snapshot of the physiological state of the organism responding to pathogenic challenges. Here we report alterations in the plasma metabolome reflecting the clinical presentation of COVID-19 patients with mild (ambulatory) diseases, moderate disease (radiologically confirmed pneumonitis, hospitalization and oxygen therapy), and critical disease (in intensive care). This analysis revealed major disease- and stage-associated shifts in the metabolome, meaning that at least 77 metabolites including amino acids, lipids, polyamines and sugars, as well as their derivatives, were altered in critical COVID-19 patient's plasma as compared to mild COVID-19 patients. Among a uniformly moderate cohort of patients who received tocilizumab, only 10 metabolites were different among individuals with a favorable evolution as compared to those who required transfer into the intensive care unit. The elevation of one single metabolite, anthranilic acid, had a poor prognostic value, correlating with the maintenance of high interleukin-10 and -18 levels. Given that products of the kynurenine pathway including anthranilic acid have immunosuppressive properties, we speculate on the therapeutic utility to inhibit the rate-limiting enzymes of this pathway including indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase.


Assuntos
COVID-19/sangue , Metaboloma , SARS-CoV-2/metabolismo , Anticorpos Monoclonais Humanizados/administração & dosagem , Biomarcadores/sangue , COVID-19/diagnóstico , Feminino , Humanos , Masculino , Metabolômica , Prognóstico , Tratamento Farmacológico da COVID-19
9.
J Neurosci ; 28(37): 9133-44, 2008 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-18784294

RESUMO

Microglia cells are the resident macrophages of the CNS, and their activation plays a critical role in inflammatory reactions associated with many brain disorders, including ischemia, Alzheimer's and Parkinson's diseases, and epilepsy. However, the changes of microglia functional properties in epilepsy have rarely been studied. Here, we used a model of status epilepticus (SE) induced by intraperitoneal kainate injections to characterize the properties of microglial cells in hippocampal slices from CX3CR1(eGFP/+) mice. SE induced within 3 h an increased expression of inflammatory mediators in the hippocampus, followed by a modification of microglia morphology, a microglia proliferation, and a significant neurodegeneration in CA1. Changes in electrophysiological intrinsic membrane properties of hippocampal microglia were detected at 24-48 h after SE with, in particular, the appearance of new voltage-activated potassium currents. Consistent with the observation of an upregulation of purinergic receptor mRNAs in the hippocampus, we also provide pharmacological evidence that microglia membrane currents mediated by the activation of P2 receptors, including P2X(7), P2Y(6), and P2Y(12), were increased 48 h after SE. As a functional consequence of this modification of purinergic signaling, motility of microglia processes toward a source of P2Y(12) receptor agonist was twice as fast in the epileptic hippocampus. This study is the first functional description of microglia activation in an in vivo model of inflammation and provides evidence for the existence of a particular microglial activation state after a status epilepticus.


Assuntos
Microglia/fisiologia , Purinas/metabolismo , Transdução de Sinais/fisiologia , Estado Epiléptico/patologia , Difosfato de Adenosina/análogos & derivados , Difosfato de Adenosina/farmacologia , Trifosfato de Adenosina/farmacologia , Animais , Receptor 1 de Quimiocina CX3C , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Eletroencefalografia , Fluoresceínas , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Técnicas In Vitro , Ácido Caínico , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Potenciais da Membrana/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Compostos Orgânicos , Técnicas de Patch-Clamp , RNA Mensageiro/metabolismo , Receptores de Quimiocinas/genética , Receptores Purinérgicos/fisiologia , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/fisiopatologia , Tionucleotídeos/farmacologia , Fatores de Tempo , Regulação para Cima/efeitos dos fármacos
11.
Cell Rep ; 21(2): 403-416, 2017 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-29020627

RESUMO

While the physiological benefits of the fibroblast growth factor 21 (FGF21) hepatokine are documented in response to fasting, little information is available on Fgf21 regulation in a glucose-overload context. We report that peroxisome-proliferator-activated receptor α (PPARα), a nuclear receptor of the fasting response, is required with the carbohydrate-sensitive transcription factor carbohydrate-responsive element-binding protein (ChREBP) to balance FGF21 glucose response. Microarray analysis indicated that only a few hepatic genes respond to fasting and glucose similarly to Fgf21. Glucose-challenged Chrebp-/- mice exhibit a marked reduction in FGF21 production, a decrease that was rescued by re-expression of an active ChREBP isoform in the liver of Chrebp-/- mice. Unexpectedly, carbohydrate challenge of hepatic Pparα knockout mice also demonstrated a PPARα-dependent glucose response for Fgf21 that was associated with an increased sucrose preference. This blunted response was due to decreased Fgf21 promoter accessibility and diminished ChREBP binding onto Fgf21 carbohydrate-responsive element (ChoRE) in hepatocytes lacking PPARα. Our study reports that PPARα is required for the ChREBP-induced glucose response of FGF21.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Glucose/metabolismo , Proteínas Nucleares/metabolismo , PPAR alfa/metabolismo , Fatores de Transcrição/metabolismo , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Células Cultivadas , Feminino , Fatores de Crescimento de Fibroblastos/genética , Hepatócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Nucleares/genética , PPAR alfa/genética , Elementos de Resposta , Fatores de Transcrição/genética
12.
PLoS One ; 4(8): e6770, 2009 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-19707551

RESUMO

BACKGROUND: Growing evidence indicates that the functional state of microglial cells differs according to the pathological conditions that trigger their activation. In particular, activated microglial cells can express sets of Kv subunits which sustain delayed rectifying potassium currents (Kdr) and modulate differently microglia proliferation and ability to release mediators. We recently reported that hippocampal microglia is in a particular activation state after a status epilepticus (SE) and the present study aimed at identifying which of the Kv channels are functionally expressed by microglia in this model. METHODOLOGY/PRINCIPAL FINDINGS: SE was induced by systemic injection of kainate in CX3CR1(eGFP/+) mice and whole cell recordings of fluorescent microglia were performed in acute hippocampal slices prepared 48 h after SE. Microglia expressed Kdr currents which were characterized by a potential of half-maximal activation near -25 mV, prominent steady-state and cumulative inactivations. Kdr currents were almost abolished by the broad spectrum antagonist 4-Aminopyridine (1 mM). In contrast, tetraethylammonium (TEA) at a concentration of 1 mM, known to block Kv3.1, Kv1.1 and 1.2 subunits, only weakly reduced Kdr currents. However, at a concentration of 5 mM which should also affect Kv1.3 and 1.6, TEA inhibited about 30% of the Kdr conductance. Alpha-dendrotoxin, which selectively inhibits Kv1.1, 1.2 and 1.6, reduced only weakly Kdr currents, indicating that channels formed by homomeric assemblies of these subunits are not important contributors of Kdr currents. Finally, agitoxin-2 and margatoxin strongly inhibited the current. CONCLUSIONS/SIGNIFICANCE: These results indicate that Kv1.3 containing channels predominantly determined Kdr currents in activated microglia after SE.


Assuntos
Hipocampo/fisiopatologia , Canal de Potássio Kv1.3/fisiologia , Microglia/fisiologia , Estado Epiléptico/fisiopatologia , Animais , Camundongos , Camundongos Endogâmicos C57BL
13.
Genes Dev ; 17(11): 1380-91, 2003 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-12782656

RESUMO

The genetic hierarchy that controls myelination of peripheral nerves by Schwann cells includes the POU domain Oct-6/Scip/Tst-1and the zinc-finger Krox-20/Egr2 transcription factors. These pivotal transcription factors act to control the onset of myelination during development and tissue regeneration in adults following damage. In this report we demonstrate the involvement of a third transcription factor, the POU domain factor Brn-2. We show that Schwann cells express Brn-2 in a developmental profile similar to that of Oct-6 and that Brn-2 gene activation does not depend on Oct-6. Overexpression of Brn-2 in Oct-6-deficient Schwann cells, under control of the Oct-6 Schwann cell enhancer (SCE), results in partial rescue of the developmental delay phenotype, whereas compound disruption of both Brn-2 and Oct-6 results in a much more severe phenotype. Together these data strongly indicate that Brn-2 function largely overlaps with that of Oct-6 in driving the transition from promyelinating to myelinating Schwann cells.


Assuntos
Diferenciação Celular/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Células de Schwann/fisiologia , Fatores de Transcrição/genética , Animais , Sequência de Bases , Diferenciação Celular/genética , Embrião de Galinha , Clonagem Molecular , Primers do DNA , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Desenvolvimento Embrionário e Fetal , Elementos Facilitadores Genéticos , Éxons , Deleção de Genes , Genes Reporter , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Camundongos , Camundongos Transgênicos , Morfogênese , Bainha de Mielina/fisiologia , Fator 6 de Transcrição de Octâmero , Fatores do Domínio POU , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas , Proteínas Recombinantes/metabolismo , Mapeamento por Restrição , Fatores de Transcrição/metabolismo , Ativação Transcricional
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA