<i>Sox10</i> is required for Schwann‐cell homeostasis and myelin maintenance in the adult peripheral nerve

Bremer, Magdalena; Fröb, Franziska; Kichko, Tatjana I.; Reeh, Peter W.; Tamm, Ernst R.; Suter, Ueli; Wegner, Michael

doi:10.1002/glia.21173

Cited by 120 publications

(126 citation statements)

References 32 publications

(46 reference statements)

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“…All these previous studies were similar to the findings of our study. SOX10 has been implicated in the late stage of neural crest cell formation, maintenance of multipotency crest cells as stem cells and specification of derivative cell fates to Schwannian and melanocytic destinations [24-26]. Mutations in the SOX10 gene have been reported in a fraction of both primary and metastatic melanoma tumors [27].…”

Section: Discussionmentioning

confidence: 99%

SOXs in human prostate cancer: implication as progression and prognosis factors

et al. 2012

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BackgroundSOX genes play an important role in a number of developmental processes. Potential roles of SOXs have been demonstrated in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and types. The aim of this study was to investigate the involvement of SOXs in the progression and prognosis of human prostate cancer (PCa).MethodsThe gene expression changes of SOXs in human PCa tissues compared with non-cancerous prostate tissues was detected using gene expression microarray, and confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohositochemistry. The roles of these genes in castration resistance were investigated in LNCaP xenograft model of PCa.ResultsThe microarray analysis identified three genes (SOX7, SOX9 and SOX10) of SOX family that were significantly dis-regulated in common among four PCa specimens. Consistent with the results of the microarray, differential mRNA and protein levels of three selected genes were found in PCa tissues by QRT-PCR analysis and immunohistochemistry. Additionally, we found that the immunohistochemical staining scores of SOX7 in PCa tissues with higher serum PSA level (P = 0.02) and metastasis (P = 0.03) were significantly lower than those with lower serum PSA level and without metastasis; the increased SOX9 protein expression was frequently found in PCa tissues with higher Gleason score (P = 0.02) and higher clinical stage (P < 0.0001); the down-regulation of SOX10 tend to be found in PCa tissues with higher serum PSA levels (P = 0.03) and advanced pathological stage (P = 0.01). Moreover, both univariate and multivariate analyses showed that the down-regulation of SOX7 and the up-regulation of SOX9 were independent predictors of shorter biochemical recurrence-free survival. Furthermore, we discovered that SOX7 was significantly down-regulated and SOX9 was significantly up-regulated during the progression to castration resistance.ConclusionsOur data offer the convince evidence that the dis-regulation of SOX7, SOX9 and SOX10 may be associated with the aggressive progression of PCa. SOX7 and SOX9 may be potential markers for prognosis in PCa patients. Interestingly, the down-regulation of SOX7 and the up-regulation of SOX9 may be important mechanisms for castration-resistant progression of PCa.

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Section: Discussionmentioning

confidence: 99%

SOXs in human prostate cancer: implication as progression and prognosis factors

et al. 2012

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“…After its role in specification (Britsch et al, 2001), it continues to be functional as Schwann cell precursors develop first into immature Schwann cells and then via promyelinating to myelinating Schwann cells. This lasting requirement has been confirmed by the analyses of mice with hypomorphic Sox10 alleles and mice in which a loxP-flanked Sox10 allele was deleted during specific stages of Schwann cell development by Cre recombinase (Schreiner et al, 2007;Finzsch et al, 2010;Bremer et al, 2011;Fröb et al, 2012). Although the essential role of Sox10 for Schwann cell development is evident, much remains to be learned about its mode of action.…”

Section: Introductionmentioning

confidence: 88%

Desert Hedgehog Links Transcription Factor Sox10 to Perineurial Development

Küspert

Weider²,

Müller³

et al. 2012

J. Neurosci.

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Schwann cells are the main glial cell type in the PNS. They develop along nerves during embryogenesis and rely on the HMG domain containing Sox10 transcription factor for specification, lineage progression, and terminal differentiation. Sox10 deletion in immature Schwann cells caused peripheral nerve defects in mice that were not restricted to this glial cell type, although expression in the nerve and gene loss were. Formation of the perineurium as the protecting sheath was, for instance, heavily compromised. This resembled the defect observed after loss of Desert hedgehog (Dhh) in mice. Here we show that Sox10 activates Dhh expression in Schwann cells via an enhancer that is located in intron 1 of the Dhh gene. Sox10 binds this enhancer in monomeric form via several sites. Mutation of these sites abolishes both Schwann-cell-specific activity and Sox10 responsiveness in vitro and in transgenic mouse embryos. This argues that Sox10 activates Dhh expression by direct binding to the enhancer and by increasing Dhh levels promotes formation of the perineurial sheath. This represents the first mechanism for a non-cell-autonomous function of Sox10 during peripheral nerve development.

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“…TRPA1 Knock-out Mice-Recording the electrically evoked CAP from isolated sciatic nerve in a three-compartment dish (34) and taking the decrease of amplitude as an index of activation by concomitant (chemical) stimulation (46), the CAP of the fast conducting myelinated fibers was not altered in any respect by superfusing the nerve for 20 min with 10 mM MG (data not shown). However, the C-fiber CAP (Fig.…”

Section: Mg Reduces Conduction Velocity and Amplitude Of The Sciatic mentioning

confidence: 95%

“…Compound Action Potential (CAP) Recordings from C-and A-fibers of Isolated Mouse Sciatic Nerves-CAP recordings were made from C-and A-fibers of isolated mouse sciatic nerves (34). Nerves from C57Bl/6 and TRPA1 knock-out mice were prepared as described above and mounted in a three-compartment chamber where they were continuously superfused with SIF at a rate of 5-7 ml/min at 37°C.…”

Section: Mouse Models-trpa1mentioning

confidence: 99%

Methylglyoxal Activates Nociceptors through Transient Receptor Potential Channel A1 (TRPA1)

Eberhardt

Filipovic

Leffler

et al. 2012

Journal of Biological Chemistry

177

174

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Background: Methylglyoxal is a reactive metabolite that modifies proteins and accumulates in diabetes and uremia. Results: Methylglyoxal excites nociceptors and releases neuropeptides via activation of TRPA1 channels by modifying their intracellular N-terminal cysteine and lysine residues. Conclusion: Methylglyoxal acting through TRPA1 is a possible cause of painful metabolic neuropathies. Significance: Methylglyoxal and its reaction with TRPA1 are promising targets for medicinal chemistry to fight neurotoxicity.

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Sox10 is required for Schwann‐cell homeostasis and myelin maintenance in the adult peripheral nerve

Cited by 120 publications

References 32 publications

SOXs in human prostate cancer: implication as progression and prognosis factors

SOXs in human prostate cancer: implication as progression and prognosis factors

Desert Hedgehog Links Transcription Factor Sox10 to Perineurial Development

Methylglyoxal Activates Nociceptors through Transient Receptor Potential Channel A1 (TRPA1)

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