Pax9's dual roles in modulating Wnt signaling during murine palatogenesis

Jia, Shihai; Zhou, Jing; D’Souza, Rena N.

doi:10.1002/dvdy.189

Cited by 15 publications

(23 citation statements)

References 36 publications

(45 reference statements)

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“…In cells depleted of PAX9, expression levels are increased for many of the mRNAs in the Wnt signaling pathway. This is consistent with previous results suggesting a role for PAX9 in the negative regulation of Wnt signaling [ 30 , 31 , 33 ].…”

Section: Resultssupporting

confidence: 94%

“…When considered as a whole, the RNA-seq dataset is enriched for several pathways known to be regulated by PAX9 (S4A In cells depleted of PAX9, expression levels are increased for many of the mRNAs in the Wnt signaling pathway. This is consistent with previous results suggesting a role for PAX9 in the negative regulation of Wnt signaling [30,31,33].…”

Section: Rna-seq Analysis Upon Pax9 Depletion Reveals Decreased Levelsupporting

confidence: 94%

“…Interestingly, increased expression of DKK1 was also found in a recent RNA-seq analysis of palatal shelves of E13.5 Pax9 -/mice [30]. PAX9 binds to a region close to the DKK1 transcription start site to repress its transcription [33]. Inhibition of Dkk1 rescues the cleft palates of Pax9 -/mice [30,33].…”

Section: Plos Geneticsmentioning

confidence: 63%

“…PAX9 binds to a region close to the DKK1 transcription start site to repress its transcription [33]. Inhibition of Dkk1 rescues the cleft palates of Pax9 -/mice [30,33]. One additional study has also suggested a role for the related EDAR/NF-κB signaling pathway in cleft palate formation in Pax9 -/mice [32].…”

Section: Plos Geneticsmentioning

confidence: 99%

“…Pax9 -/- mice also exhibit a range of cardiac malformations [ 28 ], another commonly impacted tissue in ribosomopathies [ 29 ]. While some research has been done to identify the signaling pathways regulated by PAX9, attempts to correct the developmental defects have been only partially successful [ 30 – 33 ]. Therefore, further studies are needed to identify all factors regulated by PAX9 in order to understand PAX9’s role in craniofacial development.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Paired Box 9 (PAX9), the RNA polymerase II transcription factor, regulates human ribosome biogenesis and craniofacial development

et al. 2020

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Dysregulation of ribosome production can lead to a number of developmental disorders called ribosomopathies. Despite the ubiquitous requirement for these cellular machines used in protein synthesis, ribosomopathies manifest in a tissue-specific manner, with many affecting the development of the face. Here we reveal yet another connection between craniofacial development and making ribosomes through the protein Paired Box 9 (PAX9). PAX9 functions as an RNA Polymerase II transcription factor to regulate the expression of proteins required for craniofacial and tooth development in humans. We now expand this function of PAX9 by demonstrating that PAX9 acts outside of the cell nucleolus to regulate the levels of proteins critical for building the small subunit of the ribosome. This function of PAX9 is conserved to the organism Xenopus tropicalis, an established model for human ribosomopathies. Depletion of pax9 leads to craniofacial defects due to abnormalities in neural crest development, a result consistent with that found for depletion of other ribosome biogenesis factors. This work highlights an unexpected layer of how the making of ribosomes is regulated in human cells and during embryonic development.

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Section: Resultssupporting

confidence: 94%

Section: Rna-seq Analysis Upon Pax9 Depletion Reveals Decreased Levelsupporting

confidence: 94%

Section: Plos Geneticsmentioning

confidence: 63%

Section: Plos Geneticsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Paired Box 9 (PAX9), the RNA polymerase II transcription factor, regulates human ribosome biogenesis and craniofacial development

et al. 2020

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Spatial Multiomics Reveal the Role of Wnt Modulator, Dkk2, in Palatogenesis

Oliver

Roth

Raju

et al. 2023

Preprint

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Cleft palate is a common craniofacial disorder involving multiple genetic and environmental predisposing factors. Currently, limited insight exists into the molecular mechanisms regulating osteogenic differentiation and patterning in the palate during embryogenesis. This study utilized the Pax9-deficient mouse genetic model of cleft palate to investigate the role of Pax9 in osteogenic differentiation. Single-nucleus transcriptomics and chromatin accessibility assays validated by whole-transcriptome and single-molecule spatial transcriptomics suggest a relationship between separate Pax9+ and osteogenic populations. Loss of Pax9 resulted in premature osteogenic differentiation and bone maturation. The spatially restricted osteogenic domains in Pax9-/- mice are bounded by Dkk2, which normally interfaces with Pax9 in the mesenchyme. Together, these results confirm a regulatory role for the Wnt pathway in patterning of palatal bone, offering novel insights into the complex nature of developmental signaling and osteodifferentiation in the palate.

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Tendon-associated gene expression precedes osteogenesis in mid-palatal suture establishment

Roth,

Oliver Piña,

Raju

et al. 2024

Preprint

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Orthodontic maxillary expansion relies on intrinsic mid-palatal suture mechanobiology to induce guided osteogenesis, yet establishment of the mid-palatal suture within the continuous secondary palate and causes of maxillary insufficiency remain poorly understood. In contrast, advances in cranial suture research hold promise to improve surgical repair of prematurely fused cranial sutures in craniosynostosis to potentially restore the obliterated signaling environment and ensure continual success of the intervention. We hypothesized that mid-palatal suture establishment is governed by shared principles with calvarial sutures and involves functional linkage between expanding primary ossification centres with the midline mesenchyme. We characterized establishment of the mid-palatal suture from late embryonic to early postnatal timepoints. Suture establishment was visualized using histological techniques and multimodal transcriptomics. We identified that mid-palatal suture formation depends on a spatiotemporally controlled signalling milieu in which tendon-associated genes play a significant role. We mapped relationships between extracellular matrix-encoding gene expression, tenocyte markers, and novel suture patency candidate genes. We identified similar expression patterns in FaceBase-deposited scRNA-seq datasets from cranial sutures. These findings demonstrate shared biological principles for suture establishment, providing further avenues for future development and understanding of maxillofacial interventions.

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Pax9's dual roles in modulating Wnt signaling during murine palatogenesis

Cited by 15 publications

References 36 publications

Paired Box 9 (PAX9), the RNA polymerase II transcription factor, regulates human ribosome biogenesis and craniofacial development

Paired Box 9 (PAX9), the RNA polymerase II transcription factor, regulates human ribosome biogenesis and craniofacial development

Spatial Multiomics Reveal the Role of Wnt Modulator, Dkk2, in Palatogenesis

Tendon-associated gene expression precedes osteogenesis in mid-palatal suture establishment

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