Cell fate specification during calvarial bone and suture development

Departments of Craniofacial Development and Orthodontics, Floor 27 Guy's Tower, King's College, London, SE1 9RT, UK.
Developmental Biology (Impact Factor: 3.55). 12/2007; 311(2):335-46. DOI: 10.1016/j.ydbio.2007.08.028
Source: PubMed


In this study we have addressed the fundamental question of what cellular mechanisms control the growth of the calvarial bones and conversely, what is the fate of the sutural mesenchymal cells when calvarial bones approximate to form a suture. There is evidence that the size of the osteoprogenitor cell population determines the rate of calvarial bone growth. In calvarial cultures we reduced osteoprogenitor cell proliferation; however, we did not observe a reduction in the growth of parietal bone to the same degree. This discrepancy prompted us to study whether suture mesenchymal cells participate in the growth of the parietal bones. We found that mesenchymal cells adjacent to the osteogenic fronts of the parietal bones could differentiate towards the osteoblastic lineage and could become incorporated into the growing bone. Conversely, mid-suture mesenchymal cells did not become incorporated into the bone and remained undifferentiated. Thus mesenchymal cells have different fate depending on their position within the suture. In this study we show that continued proliferation of osteoprogenitors in the osteogenic fronts is the main mechanism for calvarial bone growth, but importantly, we show that suture mesenchyme cells can contribute to calvarial bone growth. These findings help us understand the mechanisms of intramembranous ossification in general, which occurs not only during cranial and facial bone development but also in the surface periosteum of most bones during modeling and remodeling.

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    • "The modelling of cranial bones is accompanied by an increase in the brain size, which provokes their passive movement via primary displacement and relocation (Aguila and Enlow, 1998; Enlow and Hans, 1996; Francillon-Vieillot et al., 1990) until they contact one another at cranial sutures (Enlow and Hans, 1996). The sutures are formed by a fibrous connective tissue derived from the mesenchyme that exhibits the same behaviour as an ossification growth site, and the sutures grow until the brain reaches its final size (Hall, 2005; Lana-Elola et al., 2007; Mishina and Snider, 2014; Morriss-Kay and Wilkie, 2005; Opperman, 2000). Sometimes, sutures present accessory ossification centres that generate isolated bones (sutural or wormian bones, Di Ieva et al., 2013). "
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    ABSTRACT: Through ontogeny, human cranial vault bones undergo differentiation in terms of their shape, size and tissue maturation. This differentiation is visible at both the macroscopic and microscopic levels. Preliminary data from a histological and compartmentalisation exploratory analysis of individuals with different ages suggest differences in the modelling and remodelling patterns through ontogeny. Child vault bones are primarily composed of avascular lamellar bone (largely vascularised), late juvenile or adolescent bones present the largest extension of mineralised areas (highly remodelled) and the lowest vascularisation (diploe is highly reduced), and the adult present highly vascularised bone in which the diploe is again largely extended. During childhood, the existence of an avascular lamellar bone promotes the sealing of the cranium bones surfaces whereas adult vault bones seem to become opened ectocranially due to the remodelling. We discuss the possibility that both effects could be related with the head thermoregulation.
    Comptes Rendus Palevol 08/2015; In press. DOI:10.1016/j.crpv.2015.04.006 · 1.19 Impact Factor
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    • "Labeled cells do not have an ostoegenic fate, but are located in a non-osteogenic layer flanking the bone (Yoshida et al., 2008). We note, however, that when diI injections are performed at late stages in the presumptive sagittal suture, a small number of labeled cells are found in bone (Lana-Elola et al., 2007). Thus at least some sutural cells are capable of differentiating into osteoblasts. "
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    ABSTRACT: In an effort to understand the morphogenetic forces that shape the bones of the skull, we inactivated Msx1 and Msx2 conditionally in neural crest. We show that Wnt1-Cre inactivation of up to three Msx1/2 alleles results in a progressively larger defect in the neural crest-derived frontal bone. Unexpectedly, in embryos lacking all four Msx1/2 alleles, the large defect is filled in with mispatterned bone consisting of ectopic islands of bone between the reduced frontal bones, just anterior to the parietal bones. The bone is derived from neural crest, not mesoderm, and, from DiI cell marking experiments, originates in a normally non-osteogenic layer of cells through which the rudiment elongates apically. Associated with the heterotopic osteogenesis is an upregulation of Bmp signaling in this cell layer. Prevention of this upregulation by implantation of noggin-soaked beads in head explants also prevented heterotopic bone formation. These results suggest that Msx genes have a dual role in calvarial development: They are required for the differentiation and proliferation of osteogenic cells within rudiments, and they are also required to suppress an osteogenic program in a cell layer within which the rudiments grow. We suggest that the inactivation of this repressive activity may be one cause of Wormian bones, ectopic bones that are a feature of a variety of pathological conditions in which calvarial bone development is compromised.
    Developmental Biology 07/2010; 343(1-2):28-39. DOI:10.1016/j.ydbio.2010.04.007 · 3.55 Impact Factor
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    ABSTRACT: Haploinsufficiency of the transcription factor TWIST1 is associated with Saethre-Chotzen Syndrome and is manifested by craniosynostosis, which is the premature closure of the calvaria sutures. Previously, we found that Twist1 forms functional homodimers and heterodimers that have opposing activities. Our data supported a model that within the calvaria sutures Twist1 homodimers (T/T) reside in the osteogenic fronts while Twist1/E protein heterodimers (T/E) are in the mid-sutures. Twist1 haploinsufficiency alters the balance between these dimers, favoring an increase in homodimer formation throughout the sutures. The data we present here further supports this model and extends it to integrate the Twist1 dimers with the pathways that are known to regulate cranial suture patency. This data provides the first evidence of a functional link between Twist1 and the FGF pathway, and indicates that differential regulation of FGF signaling by T/T and T/E dimers plays a central role in governing cranial suture patency. Furthermore, we show that inhibition of FGF signaling prevents craniosynostosis in Twist1(+/-) mice, demonstrating that inhibition of a signaling pathway that is not part of the initiating mutation can prevent suture fusion in a relevant genetic model of craniosynostosis.
    Developmental Biology 07/2008; 318(2):323-34. DOI:10.1016/j.ydbio.2008.03.037 · 3.55 Impact Factor
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