Pax1 acts as a negative regulator of chondrocyte maturation

Takimoto, Atsushi; Mohri, Hiromi; Kokubu, Chikara; Hiraki, Yuji; Shukunami, Chisa

doi:10.1016/j.yexcr.2013.09.015

Cited by 24 publications

(34 citation statements)

References 30 publications

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“…Mutations in PAX1 cause otofaciocervical syndrome [46], characterized by facial dysmorphology, including specific nasal features such as a sunken nasal root and excessive narrowing. PAX1 plays a role in chondrocyte differentiation [47], which may explain its association with nasal width, a measure of the distance between the left and right cartilaginous nasal alae. Nevertheless, a study of Pax1 expression in mice showed expression in the pharyngeal arches at E11.5, but not in the developing olfactory placodes [48], so it is unclear how this gene influences nasal development.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology

et al. 2016

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Numerous lines of evidence point to a genetic basis for facial morphology in humans, yet little is known about how specific genetic variants relate to the phenotypic expression of many common facial features. We conducted genome-wide association meta-analyses of 20 quantitative facial measurements derived from the 3D surface images of 3118 healthy individuals of European ancestry belonging to two US cohorts. Analyses were performed on just under one million genotyped SNPs (Illumina OmniExpress+Exome v1.2 array) imputed to the 1000 Genomes reference panel (Phase 3). We observed genome-wide significant associations (p < 5 x 10−8) for cranial base width at 14q21.1 and 20q12, intercanthal width at 1p13.3 and Xq13.2, nasal width at 20p11.22, nasal ala length at 14q11.2, and upper facial depth at 11q22.1. Several genes in the associated regions are known to play roles in craniofacial development or in syndromes affecting the face: MAFB, PAX9, MIPOL1, ALX3, HDAC8, and PAX1. We also tested genotype-phenotype associations reported in two previous genome-wide studies and found evidence of replication for nasal ala length and SNPs in CACNA2D3 and PRDM16. These results provide further evidence that common variants in regions harboring genes of known craniofacial function contribute to normal variation in human facial features. Improved understanding of the genes associated with facial morphology in healthy individuals can provide insights into the pathways and mechanisms controlling normal and abnormal facial morphogenesis.

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Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology

et al. 2016

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“…This 128 amino acid long gene is essentially expressed during embryogenesis and is important for normal development of the sclerotome, pharyngeal pouches, facial mesenchyme, limbbuds, shoulder girdles and thymus [3]. Double homozygous mutants of PAX1 lead to severe vertebral defects [4].…”

Section: Introductionmentioning

confidence: 99%

Promoter methylation-independent reactivation of PAX1 by curcumin and resveratrol is mediated by UHRF1

Parashar

Capalash

2015

Clin Exp Med

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Paired box gene1 (PAX1) is essential for normal chordate development and has been recently characterised to be a tumour suppressor gene which is frequently hypermethylated in different cancer types. We investigated the reactivation of PAX1 using curcumin and resveratrol in HeLa, SiHa and Caski cell lines and role of hypermethylation in 39 CpG sites of PAX1 promoter from -6 to -286 region in regulating its expression. Curcumin in HeLa and SiHa cells and resveratrol in Caski cells caused significant (P < 0.01) reactivation of PAX1 expression as shown by qRT PCR, but reversal of promoter hypermethylation was not observed across the three cell lines. Interestingly, even positive control 5-aza-2'-deoxycytidine was not found to be effective to cause demethylation of CpG sites under consideration suggesting the promoter region to be resistant towards hypomethylating effects as shown by bisulphite sequencing. However, a striking correlation between PAX1 reactivation and Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) downregulation after treatment with curcumin and resveratrol in HeLa, SiHa and Caski cell lines was observed which was further confirmed after transient silencing of UHRF1 expression. PAX1 reexpression was also obtained in Caski and SiHa cell lines after treatment with sodium butyrate, a histone deacetylase inhibitor, suggesting that PAX1 reactivation by curcumin and resveratrol may be due to their effect on histone deacetylase mediated through downregulation of UHRF1 which can regulate both DNA methylation and histone acetylation.

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“…In Bapx1 mutants the vertebrae failed to ossify and the notochord failed to expand into nuclei pulposi . As sclerotome differentiation proceeds, gradual downregulation of Pax1 is accompanied by expression of Sox9 , which is required for chondrocyte maturation . Subsequently, Bapx1 expression is maintained by Sox9 to promote chondrogenesis and to downregulate the osteogenic regulator Runx2 …”

Section: Genes Required For Development Of the Annulus Fibrosismentioning

confidence: 99%

Developmental mechanisms of intervertebral disc and vertebral column formation

Lawson

Harfe

2017

WIREs Developmental Biology

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The vertebral column consists of repeating units of ossified vertebrae that are adjoined by fibrocartilagenous intervertebral discs. These structures form from the embryonic notochord and somitic mesoderm. In humans, congenital malformations of the vertebral column include scoliosis, kyphosis, spina bifida, and Klippel Feil syndrome. In adulthood, a common malady affecting the vertebral column includes disc degeneration and associated back pain. Indeed, recent reports estimate that low back pain is the number one cause of disability worldwide. Our review provides an overview of the molecular mechanisms underlying vertebral column morphogenesis and intervertebral disc development and maintenance, with an emphasis on what has been gleaned from recent genetic studies in mice. The aim of this review is to provide a developmental framework through which vertebral column formation can be understood so that ultimately, research scientists and clinicians alike can restore disc health with appropriately designed gene and cell-based therapies. WIREs Dev Biol 2017, 6:e283. doi: 10.1002/wdev.283 For further resources related to this article, please visit the WIREs website.

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Pax1 acts as a negative regulator of chondrocyte maturation

Cited by 24 publications

References 30 publications

Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology

Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology

Promoter methylation-independent reactivation of PAX1 by curcumin and resveratrol is mediated by UHRF1

Developmental mechanisms of intervertebral disc and vertebral column formation

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