The Osteogenic Potential of the Neural Crest Lineage May Contribute to Craniosynostosis

Doro, Daniel; Liu, Annie; Grigoriadis, Agamemnon E.; Liu, Karen

doi:10.1159/000493106

Cited by 34 publications

(31 citation statements)

References 31 publications

(26 reference statements)

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“…The contributions of neural crest cells to mouse skull vault have been studies recently . With the initiation of neural crests patterning to osteogenic lineage tracking, different transcriptional factors were found critical, such as Runx2, Osterix, Msx2, and Dlx5.…”

Section: Discussionmentioning

confidence: 99%

“…Interestedly, frontal bone‐derived osteoblasts are found less differentiated, faster growing, and faster bone nodule forming compared to parietal bone‐derived osteoblasts in vitro . Besides, frontal bone osteoblasts exhibited superior osteogenic capacities, displaying superior abilities for bone regeneration to heal damaged bone in vivo. Therefore, the skull vault is a suitable model to study osteogenic potential, and the identifications of proper targets to manipulate osteogenic potential will be valuable to treat bone defects in the clinic.…”

Section: Introductionmentioning

confidence: 99%

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Regional difference in microRNA regulation in the skull vault

Chen

Yao

et al. 2019

Developmental Dynamics

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Background The murine calvaria has several membrane bones with different tissue origins (e.g., neural crest‐derived frontal bone vs. mesoderm‐derived parietal bone). Neural crest‐derived frontal bone exhibits superior osteogenic activities and bone regeneration. MicroRNA (miRNA) has been emerged as a crucial regulator during organogenesis and is involved in a range of developmental processes. However, the underlying roles of miRNA regulation in frontal bone and parietal bone is unknown. Results Total of 83 significantly expressed known miRNAs were identified in frontal bones versus parietal bones. The significantly enriched gene ontology and KEGG pathway that were predicted by the enrichment miRNAs were involved in several biological processes (cell differentiation, cell adhesion, and transcription), and multiple osteogenic pathways (e.g., focal adhesion, MAPK, VEGF, Wnt, and insulin signaling pathway. Focal adhesion and insulin signaling pathway were selected for target verification and functional analysis, and several genes were predicted to be targets genes by the differentially expressed miRNAs, and these targets genes were tested with significant expressions. Conclusions Our results revealed a novel pattern of miRNAs in murine calvaria with dual tissue origins, and explorations of these miRNAs will be valuable for the translational studies to enhance osteogenic potential and bone regeneration in the clinic.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regional difference in microRNA regulation in the skull vault

Chen

Yao

et al. 2019

Developmental Dynamics

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“…The main difference between CNC-derived osteoblasts and mesoderm-derived osteoblasts has been demonstrated in vitro (Xu et al, 2007), namely, CNC-derived osteoblasts display robust proliferation, and the extent of the cell differentiation is much less, and the extent of bone formation is faster compared to mesoderm-derived osteoblasts, exhibiting minimal capacities of bone nodules formation in vitro (Xu et al, 2007). When mesoderm-derived osteoblasts are cultured with the addition of CNC-derived osteoblasts, the inferior performance of ossification in mesoderm-derived osteoblasts have been improved (Doro et al, 2019), suggesting that CNC input can favor the osteogenic capacities and the extent of ossification (Doro et al, 2019) (Figure 1).…”

Section: Bmp Signaling In Tissue-derived Osteoblasts the Calvarial Bomentioning

confidence: 99%

“…Ideally, a suitable cytokine or drug would be sufficient to initiate the endogenous program for bone healing. FGF and Wnt signaling are able to quicken bone healing from injury (Xu et al, 2007;Quarto et al, 2009Quarto et al, , 2010Quarto et al, , 2018Behr et al, 2010;Ichikawa et al, 2015;Li et al, 2015;Hu et al, 2017;Wu et al, 2017;Doro et al, 2019). BMPs, receptors, and intracellular Smads have robust expressions in the periosteum after a fracture, and their expressions are detectable in endothelial cells that associated with new bone formation (Yu et al, 2010).…”

Section: Bmp Signaling In Calvarial Regeneration Bmps and Calvarial Rmentioning

confidence: 99%

“…The calvaria provides important protection for the growth and formation of the brain, and its growth is concordantly orchestrated across developmental stages. Since the establishment of the dual-tissue lineages of the calvaria (Jiang et al, 2002), studies are focusing on region-dependent differential regulation of calvarial bone development (Quarto et al, 2009(Quarto et al, , 2010(Quarto et al, , 2018Wiren et al, 2011;Ichikawa et al, 2015;Li et al, 2015;Doro et al, 2019). On one hand, the region-dependent roles of evolutionally conserved signaling pathways in calvarial bones are under clarifying (Quarto et al, 2009;Behr et al, 2010;Li et al, 2010;Li et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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BMP Signaling in the Development and Regeneration of Cranium Bones and Maintenance of Calvarial Stem Cells

Chen

Yao

et al. 2020

Front. Cell Dev. Biol.

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The bone morphogenetic protein (BMP) signaling pathway is highly conserved across many species, and its importance for the patterning of the skeletal system has been demonstrated. A disrupted BMP signaling pathway results in severe skeletal defects. Murine calvaria has been identified to have dual-tissue lineages, namely, the cranial neural-crest cells and the paraxial mesoderm. Modulations of the BMP signaling pathway have been demonstrated to be significant in determining calvarial osteogenic potentials and ossification in vitro and in vivo. More importantly, the BMP signaling pathway plays a role in the maintenance of the homeostasis of the calvarial stem cells, indicating a potential clinic significance in calvarial bone and in expediting regeneration. Following the inherent evidence of BMP signaling in craniofacial biology, we summarize recent discoveries relating to BMP signaling in the development of calvarial structures, functions of the suture stem cells and their niche and regeneration. This review will not only provide a better understanding of BMP signaling in cranial biology, but also exhibit the molecular targets of BMP signaling that possess clinical potential for tissue regeneration.

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Come together over me: Cells that form the dermatocranium and chondrocranium in mice

Pitirri

Richtsmeier

Kawasaki

et al. 2023

The Anatomical Record

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Most bone develops either by intramembranous ossification where bone forms within a soft connective tissue, or by endochondral ossification by way of a cartilage anlagen or model. Bones of the skull can form endochondrally or intramembranously or represent a combination of the two types of ossification. Contrary to the classical definition of intramembranous ossification, we have previously described a tight temporo‐spatial relationship between cranial cartilages and dermal bone formation and proposed a mechanistic relationship between chondrocranial cartilage and dermal bone. Here, we further investigate this relationship through an analysis of how cells organize to form cranial cartilages and dermal bone. Using Wnt1‐Cre2 and Mesp1‐Cre transgenic mice, we determine the derivation of cells that comprise cranial cartilages from either cranial neural crest (CNC) or paraxial mesoderm (PM). We confirm a previously determined CNC‐PM boundary that runs through the hypophyseal fenestra in the cartilaginous braincase floor and identify four additional CNC‐PM boundaries in the chondrocranial lateral wall, including a boundary that runs along the basal and apical ends of the hypochiasmatic cartilage. Based on the knowledge that as osteoblasts differentiate from CNC‐ and PM‐derived mesenchyme, the differentiating cells express the transcription factor genes RUNX2 and osterix (OSX), we created a new transgenic mouse line called R2Tom. R2Tom mice carry a tdTomato reporter gene joined with an evolutionarily well‐conserved enhancer sequence of RUNX2. R2Tom mice crossed with Osx‐GFP mice yield R2Tom;Osx‐GFP double transgenic mice in which various stages of osteoblasts and their precursors are detected with different fluorescent reporters. We use the R2Tom;Osx‐GFP mice, new data on the cell derivation of cranial cartilages, histology, immunohistochemistry, and detailed morphological observations combined with data from other investigators to summarize the differentiation of cranial mesenchyme as it forms condensations that become chondrocranial cartilages and associated dermal bones of the lateral cranial wall. These data advance our previous findings of a tendency of cranial cartilage and dermal bone development to vary jointly in a coordinated manner, promoting a role for cranial cartilages in intramembranous bone formation.

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The Osteogenic Potential of the Neural Crest Lineage May Contribute to Craniosynostosis

Cited by 34 publications

References 31 publications

Regional difference in microRNA regulation in the skull vault

Regional difference in microRNA regulation in the skull vault

BMP Signaling in the Development and Regeneration of Cranium Bones and Maintenance of Calvarial Stem Cells

Come together over me: Cells that form the dermatocranium and chondrocranium in mice

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