The Protein Tyrosine Phosphatase Receptor Delta Regulates Developmental Neurogenesis

Tomita, Hideaki; Cornejo, Francisca; Aranda-Pino, Begoña; Woodard, Cameron L.; Rioseco, Constanza; Neel, Benjamin G.; Álvarez, Alejandra; Kaplan, David R.; Miller, Freda D.; Cancino, Gonzalo I.

doi:10.1016/j.celrep.2019.11.033

Cited by 61 publications

(88 citation statements)

References 68 publications

(99 reference statements)

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“…To our knowledge, however, our study is the first where genetic polymorphism in these two genes has been associated with pain sensitivity measurements. On the other hand, the four other genes in the pathway, PTPRD, DLG2, GPC6, and GRID2, have been all associated with diverse neurological disorders [31][32][33][34]. This observation supports earlier findings that neurological disorders and pain sensitivity are intimately linked [35].…”

Section: Discussionsupporting

confidence: 83%

Genome-wide association study of pain sensitivity assessed by questionnaire and the cold pressor test

Fontanillas

Kless

Bothmer

et al. 2019

Preprint

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Altered pain sensitivity is believed to play an important role in the development of chronic pain, a common debilitating condition affecting an estimated 1 of 5 adults. Pain sensitivity varies broadly between individuals, and it is notoriously difficult to measure in large population. Although pain sensitivity is known to be moderately heritable, only a limited numbers of genetics studies have been published, with limited success at identifying the genetic architecture of pain sensitivity. In this study, we deployed a pain sensitivity questionnaire (PSQ) and an at-home version of cold pressor test (CPT) in a large genotyped cohort. We performed genome-wide association study (GWAS) analysis on the PSQ scores and CPT duration, collected for 25,321 and 6,853 participants, respectively. Despite a reasonably large sample size, we identified only one genome-wide significant locus, located in the TSSC1 gene, associated with PSQ score. Genetic correlation analysis suggested that PSQ has several traits that are correlated with chronic pain states and lifestyle factors. We found that PSQ score are positively correlated to neck and shoulder pain that lasts more than 3 months and negatively correlated to acute pain sensations like fracture. Gene-based analysis followed by pathway analysis suggested that GWAS results are enriched in genes controlling Thyroid peroxidase and Melanin production. We showed that genetic variation in MC1R gene and redhead hair pigmentation is associated with an increase of pain sensitivity measured by the PSQ scores.

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Section: Discussionsupporting

confidence: 83%

Genome-wide association study of pain sensitivity assessed by questionnaire and the cold pressor test

Fontanillas

Kless

Bothmer

et al. 2019

Preprint

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“…In the present study, hsa_circ_0086354 was signi cantly down-regulated in CP plasma with an AUC of 0.967, suggesting hsa_circ_0086354 may be a promising biomarker for the early diagnosis of CP. In addition, the host gene of hsa_circ_0086354 is protein tyrosine phosphatase receptor type D (PTPRD), which is highly expressed in brain tissues and regulated neurite growth and neurons axon guidance, indicating that PTPRD and hsa_circ_0086354 might involve in CP etiology [35,36].…”

Section: Discussionmentioning

confidence: 99%

Genome-wide Analysis of Circular RNAs and Validation of hsa_circ_0086354 As a Promising Biomarker for Early Diagnosis of Cerebral Palsy

Bian

Wu³

et al. 2021

Preprint

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Background: Cerebral palsy (CP) is a spectrum of non-progressive motor disorders caused by brain injury during fetal or postnatal periods. Current diagnosis of CP mainly relies on neuroimaging and motor assessment. Here, we aimed to explore novel biomarkers for early diagnosis of CP. Methods: Blood plasma from five CP children and their healthy twin brothers/sisters was analyzed by gene microarray to screen out differentially expressed RNAs. Selected differentially expressed circular RNAs (circRNAs) were further validated using quantitative real-time PCR. Receiver operating characteristic (ROC) curve analysis was used to evaluate the value of using hsa_circ_0086354 as a biomarker of CP.Results: 43 up-regulated circRNAs and 2 down-regulated circRNAs were obtained by difference analysis (fold change>2, p<0.05), among which five circRNAs related to neuron differentiation and neurogenesis were chosen for further validation. Additional 30 pairs of CP children and healthy controls were recruited and five selected circRNAs were further detected, showing that hsa_circ_0086354 was significantly down-regulated in CP plasma compared with control, which was highly in accord with microarray analysis. ROC curve analysis showed that the area under curve (AUC) to discriminate CP children and healthy controls using hsa_circ_0086354 was 0.967, the sensitivity was 0.833 and the specificity was 0.966. Moreover, hsa_circ_0086354 was predicted as a competitive endogenous RNA for miR-181a, miR-4741 and miR-4656, and much literature evidence suggested that miR-181a may be a key target of hsa_circ_0086354 to regulate neuronal survival and neuronal differentiation. Conclusion: Hsa_circ_0086354 was significantly down-regulated in blood plasma of CP children, which may be a novel competent biomarker for early diagnosis of CP.

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“…Murine cortical precursor cells were cultured as described previously (Barnabe-Heider and Miller, 2003; Tomita et al, 2020). Briefly, mouse cortical precursor cells from cortices were dissected from E12.5 wild-type or Dhcr7-KO mouse embryos in ice-cold HBSS (Invitrogen) and transferred into cortical precursor medium.…”

Section: Methodsmentioning

confidence: 99%

“…E13.5 cortices from Dhcr7 +/+ or Dhcr7 -/- embryos were dissected and mechanically dissociated into a single cell suspension by fire-polished glass pipette as previously described (Capecchi and Pozner, 2015; Tomita et al, 2020). Cell density and viability were determined using trypan blue exclusion.…”

Section: Methodsmentioning

confidence: 99%

7-Dehydrocholesterol-derived oxysterols cause neurogenic defects in Smith-Lemli-Opitz syndrome

Tomita

et al. 2021

Preprint

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Defective 3β-hydroxysterol-Δ7 −reductase (DHCR7) in the developmental disorder, Smith-Lemli-Opitz syndrome (SLOS), results in deficiency in cholesterol and accumulation of its precursor, 7-dehydrocholesterol (7-DHC). Here, we show that loss of DHCR7 causes accumulation of 7-DHC-derived oxysterol metabolites, premature neurogenesis, and perturbation of neuronal localization in developing murine or human cortical neural precursors, both in vitro and in vivo. We found that a major oxysterol, 3β,5α-dihydroxycholest-7-en-6-one (DHCEO), mediates these effects by initiating crosstalk between glucocorticoid receptor (GR) and neurotrophin receptor kinase TrkB. Either loss of DHCR7 or direct exposure to DHCEO causes hyperactivation of GR and TrkB and their downstream MEK-ERK-C/EBP signaling pathway in cortical neural precursors. Moreover, direct inhibition of GR activation with an antagonist or inhibition of DHCEO accumulation with antioxidants rescues the premature neurogenesis phenotype caused by the loss of DHCR7. These results suggest that GR could be a new therapeutic target against the neurological defects observed in SLOS.

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The Protein Tyrosine Phosphatase Receptor Delta Regulates Developmental Neurogenesis

Cited by 61 publications

References 68 publications

Genome-wide association study of pain sensitivity assessed by questionnaire and the cold pressor test

Genome-wide association study of pain sensitivity assessed by questionnaire and the cold pressor test

Genome-wide Analysis of Circular RNAs and Validation of hsa_circ_0086354 As a Promising Biomarker for Early Diagnosis of Cerebral Palsy

7-Dehydrocholesterol-derived oxysterols cause neurogenic defects in Smith-Lemli-Opitz syndrome

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