An <i>in situ</i> hybridization study of Runx2, Osterix, and Sox9 at the onset of condylar cartilage formation in fetal mouse mandible

Shibata, Shunichi; Suda, Naoto; Suzuki, Shigehiko; Fukuoka, Hiroki; Yamashita, Yasuo

doi:10.1111/j.1469-7580.2006.00525.x

Cited by 66 publications

(106 citation statements)

References 38 publications

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“…Some of these markers are known to be expressed in both chondrogenic and osteogenic cells, especially at early developmental points. In particular, Runx2 is known to be expressed in, and to be important for the differentiation of, early chondrocytes as well as osteoblasts, whereas Sox9 is known to be expressed in common progenitors of both cartilage and bone (Stricker et al, 2002;Akiyama et al, 2005;Shibata et al, 2006). However, the particular combinations of markers that we examined were highly diagnostic of the specific bone versus cartilage cell identity.…”

Section: Expression Of Molecular Markers During the Development Of Dementioning

confidence: 63%

“…Each of these steps is characterized by the expression of discrete sets of molecular markers. All chondrocytes of the trunk skeleton express the Coll II (also known as Col2a1 and Col II) gene, encoding collagen type II, and the transcription factor Sox9 (Kronenberg, 2003;Harada and Roden, 2003;Zelzer and Olsen, 2003;Yamashiro et al, 2004;Aberg et al, 2005;Shibata et al, 2006). As the skeletal elements mature and growth plates form towards their distal ends, these two genes continue to be expressed at high levels in both proliferating and resting chondrocytes, whereas Sox9 is downregulated during the transition to the hypertrophic chondrocytes.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of skeletogenic differentiation in cranial dermal bone

et al. 2007

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Although endochondral ossification of the limb and axial skeleton is relatively well-understood, the development of dermal (intramembranous) bone featured by many craniofacial skeletal elements is not nearly as well-characterized. We analyzed the expression domains of a number of markers that have previously been associated with endochondral skeleton development to define the cellular transitions involved in the dermal ossification process in both chick and mouse. This led to the recognition of a series of distinct steps in the dermal differentiation pathways, including a unique cell type characterized by the expression of both osteogenic and chondrogenic markers. Several signaling molecules previously implicated in endochondrial development were found to be expressed during specific stages of dermal bone formation. Three of these were studied functionally using retroviral misexpression. We found that activity of bone morphogenic proteins (BMPs) is required for neural crest-derived mesenchyme to commit to the osteogenic pathway and that both Indian hedgehog (IHH) and parathyroid hormone-related protein (PTHrP, PTHLH) negatively regulate the transition from preosteoblastic progenitors to osteoblasts. These results provide a framework for understanding dermal bone development with an aim of bringing it closer to the molecular and cellular resolution available for the endochondral bone development.

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Section: Expression Of Molecular Markers During the Development Of Dementioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Regulation of skeletogenic differentiation in cranial dermal bone

et al. 2007

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“…This finding is likely due to the fact that PTHrP expression and cell proliferation are quite low in the polymorphic progenitor cell layer, rendering it unable to supply a sufficient number of chondroprogenitor cells and chondrocytes for condyle's appositional growth (Luder et al, 1988;Rabie and Hagg, 2002;Shibata et al, 2006). These data and interpretation suggest that the Ihh-PTHrP regulatory loop, originally suggested to operate between prehypertrophic and peri-articular chondrocytes in developing long bones Lanske et al, 1996), would normally operate equally well between Ihh-expressing condylar chondrocytes and Sox9-expressing polymorphic layer progenitor cells, pointing to its dexterity and versatility also suggested by our recent study on cranial base synchondroses (Young et al, 2006).…”

Section: Ihhmentioning

confidence: 84%

“…In mammalian embryos, the first overt step in mandibular condyle development is the appearance of an ecto-mesenchymal cell condensation at the supralateral distal site of the jaw anlagen (Helms and Schneider, 2003;Shibata et al, 2006). The condyle condensation faces the developing temporal bone, but at this early stage, there is no obvious sign of an intervening articular disc primordium.…”

Section: Introductionmentioning

confidence: 99%

Temporomandibular joint formation and condyle growth require Indian hedgehog signaling

Shibukawa¹,

Young²,

Wu³

et al. 2006

Developmental Dynamics

127

174

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The temporomandibular joint (TMJ) is essential for jaw function, but the mechanisms regulating its development remain poorly understood. Because Indian hedgehog (Ihh) regulates trunk and limb skeletogenesis, we studied its possible roles in TMJ development. In wild-type mouse embryos, Ihh expression was already strong in condylar cartilage by embryonic day (E) 15.5, and expression of Ihh receptors and effector genes (Gli1, Gli2, Gli3, and PTHrP) indicated that Ihh range of action normally reached apical condylar tissue layers, including polymorphic chondroprogenitor layer and articular disc primordia. In Ihh ؊/؊ embryos, TMJ development was severely compromised. Condylar cartilage growth, polymorphic cell proliferation, and PTHrP expression were all inhibited, and growth plate organization and chondrocyte gene expression patterns were abnormal. These severe defects were partially corrected in double Ihh ؊/؊ /Gli3؊/؊ mutants, signifying that Ihh action is normally modulated and delimited by Gli3 and Gli3 R in particular. Both single and double mutants, however, failed to form an articular disc primordium, normally appreciable as an independent condensation between condylar apex and neighboring developing temporal bone in wild-type. This failure persisted at later stages, leading to complete absence of a normal functional disc and lubricin-expressing joint cavities. In summary, Ihh is very important for TMJ development, where it appears to regulate growth and elongation events, condylar cartilage phenotype, and chondroprogenitor cell function. Absence of articular disc and joint cavities in single and double mutants points to irreplaceable Ihh roles in formation of those critical TMJ components. Developmental Dynamics 236:426 -434, 2007.

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“…Runx2 knockout mice do not form the condylar cartilage, which suggests a role for RUNX2 protein in its differentiation (Shibata et al, 2004(Shibata et al, , 2006. This cartilage may be derived either from the periosteum of the dentary or from a sesamoid that is independent from the rest of the developing jaw (reviewed in Hall, 2005, p 155-159).…”

Section: The Evolution Of Cartilage Differentiationmentioning

confidence: 99%

Runx2 is essential for larval hyobranchial cartilage formation in Xenopus laevis

Kerney

Gross

Howard

2007

Developmental Dynamics

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The vertebrate transcription factor protein Runx2 is regarded as a "master regulator" of bone formation due to the dramatic loss of the osseous skeleton in the mouse homozygous knockout. However, Runx2 mRNA also is expressed in the pre-hypertrophic cartilaginous skeleton of the mouse and chicken, where its developmental function is largely unknown. Several tiers of Runx2 regulation exist in the mouse, any of which may account for its seeming biological inactivity during early stages of skeletogenesis. Unlike mouse and chicken, zebrafish require Runx2 function in early cartilage differentiation. The present study reveals that the earlier functional role of Runx2 in cartilage differentiation is shared between zebrafish and Xenopus. A combination of morpholino oligonucleotide injections and neural crest transplants indicate that Runx2 is involved in differentiation of the cartilaginous hyobranchial skeleton in the frog, Xenopus laevis. Additionally, in situ hybridizations show runx2 mRNA expression in mesenchymal precursors of the cartilaginous skull, which reveals the earliest pre-patterning of these cartilages described to date. The early distribution of runx2 resolves the homology of the larval suprarostral plate, which is one of the oldest controversies of anuran skull development. Together these data reveal a shift in Runx2 protein function during vertebrate evolution towards its exclusive roles in cartilage hypertrophy and bone differentiation within the amniote lineage. Developmental Dynamics 236:1650 -1662, 2007.

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An in situ hybridization study of Runx2, Osterix, and Sox9 at the onset of condylar cartilage formation in fetal mouse mandible

Cited by 66 publications

References 38 publications

Regulation of skeletogenic differentiation in cranial dermal bone

Regulation of skeletogenic differentiation in cranial dermal bone

Temporomandibular joint formation and condyle growth require Indian hedgehog signaling

Runx2 is essential for larval hyobranchial cartilage formation in Xenopus laevis

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