Znf385C mediates a novel p53-dependent transcriptional switch to control timing of facial bone formation

Hochgreb-Hägele, Tatiana; Koo, Daniel E. S.; Bronner‐Fraser, Marianne

doi:10.1016/j.ydbio.2015.01.011

Cited by 13 publications

(5 citation statements)

References 34 publications

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“…Knocking out Mdm2 in osteoblasts significantly impaired murine bone formation, indicating that Mdm2 modulates p53 during in vivo bone development . Additionally, Znf385C was recently reported to mediate a p53‐dependent developmental switch in facial bone formation . Furthermore, Recql4 is a critical modulator of p53 activity during in vivo skeletogenesis, and a conditional Recql4 knockout in the skeletal lineage developed limb abnormalities and craniosynostosis .…”

Section: Discussionmentioning

confidence: 99%

Bre Enhances Osteoblastic Differentiation by Promoting the Mdm2-Mediated Degradation of p53

Jin

Wang

et al. 2017

Stem Cells

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Bre is a conserved cellular protein expressed in various tissues. Its major function includes DNA damage repair and anti-apoptosis. Recent studies indicate that Bre is potentially involved in stem cell differentiation although pathophysiological significance along with the molecular mechanisms is still unclear. Here, we report that Bre protein was substantially expressed in the bone tissue and its expression was highly upregulated during the osteogenic differentiation. To test a hypothesis that Bre plays functional roles in the process of osteogenic differentiation, we examined the expression of Bre in an osteoporosis mouse model. Compared with the normal bone tissue, Bre expression in osteoporotic bone was also significantly reduced. Moreover, knockdown of Bre in the mouse bone marrow mesenchymal cells significantly reduced the expression of osteogenic marker genes, the alkaline phosphatase activity, and the mineralization capacity, while overexpression of Bre greatly promoted the osteogenesis both in vitro and in vivo. Interestingly, we founded that knockdown of Bre led to activation of the p53 signaling pathways exhibited by increased p53, p21, and Mdm2. However, when we inhibited the p53 by siRNA silencing or pifithrin-α, the impaired osteogenesis caused by Bre knockdown was greatly restored. Finally, we found that Bre promoted the Mdm2-mediated p53 ubiquitination and degradation by physically interacting with p53. Taken together, our results revealed a novel function of Bre in osteoblast differentiation through modulating the stability of p53. Stem Cells 2017;35:1760-1772.

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Section: Discussionmentioning

confidence: 99%

Bre Enhances Osteoblastic Differentiation by Promoting the Mdm2-Mediated Degradation of p53

Jin

Wang

et al. 2017

Stem Cells

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“…Despite the histological similar appearance of the mesoderm- and CNCC-derived bones, the CNCC-derived bones of the jaw for example differ biologically; they possess distinct gene expression signatures, higher alkaline phosphatase activity, higher proliferation and greater regenerative capabilities (Heuze et al, 2014; Hochgreb-Hagele et al, 2015; Ichikawa et al, 2015; Quarto et al, 2010). Identifying the role of local signaling pathways that help to properly develop these cartilage structures is critical to the understanding of the precise shape and size that bones acquire, a requisite for their function.…”

Section: Introductionmentioning

confidence: 99%

Distinct requirements of wls , wnt9a , wnt5b and gpc4 in regulating chondrocyte maturation and timing of endochondral ossification

Ling

Rochard

Liao

2017

Developmental Biology

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Formation of the mandible requires progressive morphologic change, proliferation, differentiation and organization of chondrocytes preceding osteogenesis. The Wnt signaling pathway is involved in regulating bone development and maintenance. Chondrocytes that are fated to become bone require Wnt to polarize and orientate appropriately to initiate the endochondral ossification program. Although the canonical Wnt signaling has been well studied in the context of bone development, the effects of non-canonical Wnt signaling in regulating the timing of cartilage maturation and subsequent bone formation in shaping ventral craniofacial structure is not fully understood.. Here we examined the role of the non-canonical Wnt signaling pathway (wls, gpc4, wnt5b and wnt9a) in regulating zebrafish Meckel’s cartilage maturation to the onset of osteogenic differentiation. We found that disruption of wls resulted in a significant loss of craniofacial bone, whereas lack of gpc4, wnt5b and wnt9a resulted in severely delayed endochondral ossification. This study demonstrates the importance of the non-canonical Wnt pathway in regulating coordinated ventral cartilage morphogenesis and ossification.

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“…As a second example, zinc-finger 385 family genes including ZNF385B/C/D were also selectively expressed in cartilage and another family member, ZNF385A, was also highly expressed in the tissue (Additional file 3 : Dataset S2). Fluorescence-labeled Znf385C protein was highly expressed in maturing chondrocytes in the pharyngeal arches as well as in the cartilage associated with the ear and ventral fins in zebrafish [ 69 ]. Loss of Znf385C in zebrafish led to craniofacial defects and premature ossification of the Meckel’s cartilage, potentially through disturbance of p53-dependent cell cycle regulation [ 69 ].…”

Section: Discussionmentioning

confidence: 99%

“…Fluorescence-labeled Znf385C protein was highly expressed in maturing chondrocytes in the pharyngeal arches as well as in the cartilage associated with the ear and ventral fins in zebrafish [ 69 ]. Loss of Znf385C in zebrafish led to craniofacial defects and premature ossification of the Meckel’s cartilage, potentially through disturbance of p53-dependent cell cycle regulation [ 69 ]. Therefore, targeting some of the 94 understudied CS genes is likely to reveal new biology related to cartilage function.…”

Section: Discussionmentioning

confidence: 99%

Genes uniquely expressed in human growth plate chondrocytes uncover a distinct regulatory network

Balasubramanian

Krakow

et al. 2017

BMC Genomics

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BackgroundChondrogenesis is the earliest stage of skeletal development and is a highly dynamic process, integrating the activities and functions of transcription factors, cell signaling molecules and extracellular matrix proteins. The molecular mechanisms underlying chondrogenesis have been extensively studied and multiple key regulators of this process have been identified. However, a genome-wide overview of the gene regulatory network in chondrogenesis has not been achieved.ResultsIn this study, employing RNA sequencing, we identified 332 protein coding genes and 34 long non-coding RNA (lncRNA) genes that are highly selectively expressed in human fetal growth plate chondrocytes. Among the protein coding genes, 32 genes were associated with 62 distinct human skeletal disorders and 153 genes were associated with skeletal defects in knockout mice, confirming their essential roles in skeletal formation. These gene products formed a comprehensive physical interaction network and participated in multiple cellular processes regulating skeletal development. The data also revealed 34 transcription factors and 11,334 distal enhancers that were uniquely active in chondrocytes, functioning as transcriptional regulators for the cartilage-selective genes.ConclusionsOur findings revealed a complex gene regulatory network controlling skeletal development whereby transcription factors, enhancers and lncRNAs participate in chondrogenesis by transcriptional regulation of key genes. Additionally, the cartilage-selective genes represent candidate genes for unsolved human skeletal disorders.Electronic supplementary materialThe online version of this article (10.1186/s12864-017-4378-y) contains supplementary material, which is available to authorized users.

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Znf385C mediates a novel p53-dependent transcriptional switch to control timing of facial bone formation

Cited by 13 publications

References 34 publications

Bre Enhances Osteoblastic Differentiation by Promoting the Mdm2-Mediated Degradation of p53

Bre Enhances Osteoblastic Differentiation by Promoting the Mdm2-Mediated Degradation of p53

Distinct requirements of wls , wnt9a , wnt5b and gpc4 in regulating chondrocyte maturation and timing of endochondral ossification

Genes uniquely expressed in human growth plate chondrocytes uncover a distinct regulatory network

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