Wnt Signaling Upregulates Teneurin-3 Expression via Canonical and Non-canonical Wnt Pathway Crosstalk

Bastías-Candia, Sussy; Martínez, Milka; Zolezzi, Juan M.; Inestrosa, Nibaldo C.

doi:10.3389/fnins.2019.00505

Cited by 10 publications

(9 citation statements)

References 55 publications

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“…This work not only demonstrate the involvement of Wnt signaling in regulating Ten-3 expression but also revealed that Wnt3a (a canonical Wnt ligand) increases the expression of Ten-3 through a mechanism dependent on the secretion and activity of Wnt5a (a noncanonical ligand). Although the work raises new questions, the results seem to demonstrate the upregulation of Ten-3 by Wnt signaling and suggest that Ten-3 modulation is possible because of crosstalk between the canonical and noncanonical Wnt pathways (52).…”

Section: Discussionmentioning

confidence: 92%

Morphological Neurite Changes Induced by Porcupine Inhibition Are Rescued by Wnt Ligands

Godoy

Espinoza-Caicedo

Inestrosa

2020

Preprint

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Background: Wnt signaling plays key roles in cellular and physiological processes, including cell proliferation, differentiation and migration during development and tissue homeostasis in adults. This pathway can be defined as Wnt/β-catenin-dependent or β-catenin-independent or "non-canonical", both signaling are involved in neurite and synapse development/maintenance. Porcupine (PORCN), an acylase that o-acylates Wnt ligands, a major modification in secretion and interaction with its receptors. We use Wnt-C59, a specific PORCN inhibitor, to block the secretion of endogenous Wnts in young hippocampal neurons (DIV 4). Under these conditions, the morphology and length of the neurites and the complexity of the dendritic tree and axonal polarity were evaluated. Methods: Cultured primary young hippocampal neurons obtained from Sprague-Dawley rat fetuses (E18), were cultured until day in vitro (DIV) 4 (according to Banker´s protocol) and treated with Wnt-C59 for 24h, Wnt ligands were added to the cultures on DIV 3 for 24h. Dendritic arbors and neurites were analysis by fluorescence microscopy. Transfection with Lipofectamine 2000 on DIV 2 of plasmid expressing eGFP and KIF5-Cherry and neurons were fixed on DIV 4. Immunostaining was performed with MAP1B and Tau protein. Immunoblot analysis was carried out with Wnt3a, b-catenin and GSK-3b (p-Ser9). Quantitative analysis of dendrite morphology was carried out with ImageJ (NIH) software with Neuron J Plugin.Results: We report, here, that Wnt-C59 treatment changed the morphology of the dendritic arbors and neurites of young hippocampal neurons, with decreases -catenin and Wnt3a and an increase in GSK-3 (p-Ser9) levels No effect was observed on axonal polarity. In sister cultures, addition of exogenous Wnt3a, 5a and 7a ligands rescued the changes in neuronal morphology. Wnt3a restored the length of neurites to near that of the control, but Wnt7a increased the neurite length beyond that of the control. Wnt5a also restored the length of neurites relative Wnt concentrations. Conclusions: Our results indicated that all 3 Wnt ligands restored dendritic arbor complexity with recovery of secondary and tertiary projections in young hippocampal neurons. We proposed that PORCN is an emerging molecular target of interest in the search for preclinical options to study and treat neurological diseases.

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Section: Discussionmentioning

confidence: 92%

Morphological Neurite Changes Induced by Porcupine Inhibition Are Rescued by Wnt Ligands

Godoy

Espinoza-Caicedo

Inestrosa

2020

Preprint

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“…Teneurin 3 belongs to a highly conserved family of proteins and is necessary for various functions, including cell adhesion, cytoskeleton interaction, and calcium binding [ 17 , 18 ]. Previous studies revealed a novel mutation in TENM3 (OMIM * 610083) , which co-segregated in all severely affected members in a three-generation family from Philadelphia.…”

Section: Discussionmentioning

confidence: 99%

Replicative verification of susceptibility genes previously identified from families with segregating developmental dysplasia of the hip

Wang²,

Chen

et al. 2021

Ital J Pediatr

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Background Developmental dysplasia of the hip (DDH) is a complex hip joint deformity with effects ranging from acetabulum malformation to irreversible hip dislocation. Previous studies suggest a significant association of four variations, teneurin transmembrane protein 3 (TENM3, OMIM * 610083) (chr4:183721398), heparan sulfate proteoglycan 2 (HSPG2, OMIM * 142461) (chr1:22201470), ATPase plasma membrane Ca2+ transporting 4 (ATP2B4, OMIM * 108732) (chr1:203682345), and prostaglandin F receptor (PTGFR, OMIM * 600563) (chr1:79002214), with DDH susceptibility in families with segregating DDH. However, the association was not validated in sporadic cases and remains controversial. To confirm the association of the reported variations in these four genes with DDH, we conducted replicative verification in 250 sporadic samples with DDH from a Chinese Han population. Methods We conducted Sanger sequencing after amplifying the variation sites. The results were compared with the reference sequence from the GRCh37 assembly in UCSC (http://genome.ucsc.edu). Results Replication analysis of 250 sporadic samples by Sanger sequencing indicated that the four variations, TENM3 (OMIM * 610083, chr4:183721398), HSPG2 (OMIM * 142461, chr1:22201470), ATP2B4 (OMIM * 108732, chr1:203682345), and PTGFR (OMIM * 600563, chr1:79002214), were not associated with the susceptibility to DDH in the Chinese Han population. Conclusions Further studies should be performed to identify other variations of these four genes that are potentially associated with DDH by whole-exome sequencing and the results should be verified in different populations.

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“…WNT3A, β-catenin, and pGSK3β are components of the Wnt signaling pathway [ 24 ], and the activation of this pathway reportedly induces EndoMT [ 24 , 25 ]. WNT3A is a Wnt protein that activates the canonical Wnt pathway and to be bioactive as determined by TCF/LEF [ 26 ]. WNT3A involved in neural crest cell differentiation and hCECs are derived from neural crest [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of SOX2 Repression on Corneal Endothelial Cells

Hwang

Shin

2020

IJMS

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Purpose: Human corneal endothelial cells (hCECs) pump out water from the stroma and maintain the clarity of the cornea. The sex-determining region Y-box 2 (SOX2) participates in differentiation during the development of the anterior segment of the eye and is found in the periphery of wounded corneas. This study was performed to investigate the effect of SOX2 repression on hCECs. Methods: Cultured hCECs were transfected by siRNA for SOX2. The wound healing rate and cell viability were measured. The cell proliferation-associated protein level was evaluated by Western blotting and RT-PCR. The energy production and mitochondrial function were measured, and cell shape and WNT signaling were assessed. Results: Upon transfecting the cultured cells with siRNA for SOX2, the SOX2 level was reduced by 80%. The wound healing rate and viability were also reduced. Additionally, CDK1, cyclin D1, SIRT1, and ATP5B levels were reduced, and CDKN2A and pAMPK levels were increased. Mitochondrial oxidative stress and mitochondrial viability decreased, and the cell shape became elongated. Furthermore, SMAD1, SNAI1, WNT3A, and β-catenin levels were increased. Conclusion: SOX2 repression disrupts the normal metabolism of hCECs through modulating WNT signaling and mitochondrial functions.

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Wnt Signaling Upregulates Teneurin-3 Expression via Canonical and Non-canonical Wnt Pathway Crosstalk

Cited by 10 publications

References 55 publications

Morphological Neurite Changes Induced by Porcupine Inhibition Are Rescued by Wnt Ligands

Morphological Neurite Changes Induced by Porcupine Inhibition Are Rescued by Wnt Ligands

Replicative verification of susceptibility genes previously identified from families with segregating developmental dysplasia of the hip

Effect of SOX2 Repression on Corneal Endothelial Cells

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