Pax6 Expressed in Osteocytes Inhibits Canonical Wnt Signaling

Jami, Ajita; Gadi, Jogeswar; Lee, Min Jung; Kim, Eun Jin; Lee, Mi‐Jeong; Jung, Han Sung; Kim, Hong Hee; Lim, Sung Kil

doi:10.1007/s10059-013-2310-0

Cited by 12 publications

(8 citation statements)

References 37 publications

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“…The affected individuals showed half of the correlation (R 2 = 0.0522) between face height and CI that their non-affected relatives did (R 2 = 0.1069). These results seem to be consistent with the role of PAX6 in the spatial expression of neurocranial osteocytes, but not facial osteocytes, found in other studies (17). Together, this evidence suggests that the more brachycephalic head shape observed in affected individuals may be a result of the PAX6 splicesite mutation.…”

Section: Discussionsupporting

confidence: 91%

“…Further, previous work in the field identified a subject with a compound heterozygous PAX6 mutation that presented with severe bilateral microphthalmia and extreme microcephaly . Jami et al found that pax6 was expressed exclusively in the calvaria and long bone tissues during mouse development. These results indicate that PAX6 might play a central role in stimulating the differentiation of mature osteoblasts to osteocytes in calvaria bones.…”

Section: Discussionmentioning

confidence: 99%

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Ocular and craniofacial phenotypes in a large Brazilian family with congenital aniridia

et al. 2014

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Congenital aniridia is a rare genetic disorder characterized by varying degrees of iris hypoplasia that are associated with additional ocular abnormalities. More than 90% of the causal mutations identified are found in the PAX6 gene, a transcription factor of critical importance in the process of neurogenesis and ocular development. Here, we investigate clinical, molecular, and craniofacial features of a large Brazilian family with congenital aniridia. Among the 56 eyes evaluated, phenotype variation encompassed bilateral total aniridia to mild iris defects with extensive variation between eyes of the same individual. PAX6 molecular screening indicated a heterozygous splice mutation (c.141 + 1G>A). Thus, we hypothesize that this splicing event may cause variation in the expression of the wild-type transcript, which may lead to the observed variation in phenotype. Affected individuals were more brachycephalic, even though their face height and cephalic circumference were not significantly different when compared to those of non-affected relatives. From this, we infer that the head shape of affected subjects may also be a result of the PAX6 splice-site mutation. Our data summarize the clinical variability associated with the ocular phenotype in a large family with aniridia, and help shed light on the role of PAX6 in neurocranial development.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Ocular and craniofacial phenotypes in a large Brazilian family with congenital aniridia

et al. 2014

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“…In the Wnt signaling study, MC3T3-E1 cells were transfected as previously reported 25. Seeded cells were treated in different concentrations (50 nM, 500 nM, 5 µM) of oligopeptide along with Wnt7a and DKK1 for 24 hours.…”

Section: Methodsmentioning

confidence: 99%

Cyclized Oligopeptide Targeting LRP5/6-DKK1 Interaction Reduces the Growth of Tumor Burden in a Multiple Myeloma Mouse Model

et al. 2017

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PurposeDickkopf 1 (DKK1) has been extensively investigated in mouse models of multiple myeloma, which results in osteolytic bone lesions. Elevated DKK1 levels in bone marrow plasma and serum inhibit the differentiation of osteoblast precursors. Present pharmaceutical approaches to target bone lesions are limited to antiresorptive agents. In this study, we developed a cyclized oligopeptide against DKK1-low density lipoprotein receptor-related protein (LRP) 5/6 interaction and tested the effects of the oligopeptide on tumor burden.Materials and MethodsA cyclized oligopeptide based on DKK1-LRP5/6 interactions was synthesized chemically, and its nuclear magnetic resonance structure was assessed. Luciferase reporter assay and mRNA expressions of osteoblast markers were evaluated after oligopeptide treatment. MOPC315.BM.Luc cells were injected into the tail vein of mice, after which cyclized oligopeptide was delivered subcutaneously 6 days a week for 4 weeks.ResultsThe cyclized oligopeptide containing NXI motif bound to the E1 domain of LRP5/6 effectively on surface plasmon resonance analysis. It abrogated the Wnt-β-catenin signaling inhibited by DKK1, but not by sclerostin, dose dependently. RT-PCR and alkaline phosphatase staining showed increased expressions of osteoblast markers according to the treatment concentrations. Bioluminescence images showed that the treatment of cyclized oligopeptide reduced tumor burden more in oligopeptide treated group than in the vehicle group.ConclusionThe cyclized oligopeptide reported here may be another option for the treatment of tumor burden in multiple myeloma.

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“…Pax6 is expressed in the developing retina, lens and cornea, and continues to be expressed in several mature ocular cell types [ 2 – 6 ]. Pax6 is also expressed in the developing and mature endocrine pancreas [ 7 , 8 ], central nervous system (CNS), and olfactory system [ 2 , 3 , 9 ], gut [ 10 ] and osteocytes [ 11 ]. In the complete absence of Pax6 , eyes and nasal structures fail to develop [ 12 – 14 ], and patterning in the forebrain and specification of hormone-producing cells in the endocrine pancreas are severely perturbed [ 7 , 8 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Mapping the Pax6 3’ untranslated region microRNA regulatory landscape

et al. 2018

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BackgroundPAX6 is a homeodomain transcription factor that acts in a highly dosage-sensitive manner to regulate the development and function of the eyes, nose, central nervous system, gut, and endocrine pancreas. Several individual microRNAs (miRNA) have been implicated in regulating PAX6 in different cellular contexts, but a more general view of how they contribute to the fine-tuning and homeostasis of PAX6 is poorly understood.ResultsHere, a comprehensive analysis of the Pax6 3′ untranslated region was performed to map potential miRNA recognition elements and served as a backdrop for miRNA expression profiling experiments to identify potential cell/tissue-specific miRNA codes. Pax6 3’UTR pull-down studies identified a cohort of miRNA interactors in pancreatic αTC1–6 cells that, based on the spacing of their recognition sites in the Pax6 3’UTR, revealed 3 clusters where cooperative miRNA regulation may occur. Some of these interacting miRNAs have been implicated in α cell function but have not previously been linked to Pax6 function and may therefore represent novel PAX6 regulators.ConclusionsThese findings reveal a regulatory landscape upon which miRNAs may participate in the developmental control, fine-tuning and/or homeostasis of PAX6 levels.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5212-x) contains supplementary material, which is available to authorized users.

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Pax6 Expressed in Osteocytes Inhibits Canonical Wnt Signaling

Cited by 12 publications

References 37 publications

Ocular and craniofacial phenotypes in a large Brazilian family with congenital aniridia

Ocular and craniofacial phenotypes in a large Brazilian family with congenital aniridia

Cyclized Oligopeptide Targeting LRP5/6-DKK1 Interaction Reduces the Growth of Tumor Burden in a Multiple Myeloma Mouse Model

Mapping the Pax6 3’ untranslated region microRNA regulatory landscape

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