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On the evolutionary relationship between chondrocytes and osteoblasts.

Gómez-Picos P, Eames BF - Front Genet (2015)

Bottom Line: Emphasizing an embryological and evolutionary transcriptomic view, we hypothesize that the Runx2 GRN underlying bone formation was co-opted from mature cartilage.We discuss how modern molecular genetic experiments, such as comparative transcriptomics, can test this hypothesis directly, meanwhile permitting levels of constraint and adaptation to be evaluated quantitatively.Therefore, comparative transcriptomics may revolutionize understanding of not only the clade-specific evolution of skeletal cells, but also the generation of evolutionary novelties, providing a modern paradigm for the evolutionary process.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, SK Canada.

ABSTRACT
Vertebrates are the only animals that produce bone, but the molecular genetic basis for this evolutionary novelty remains obscure. Here, we synthesize information from traditional evolutionary and modern molecular genetic studies in order to generate a working hypothesis on the evolution of the gene regulatory network (GRN) underlying bone formation. Since transcription factors are often core components of GRNs (i.e., kernels), we focus our analyses on Sox9 and Runx2. Our argument centers on three skeletal tissues that comprise the majority of the vertebrate skeleton: immature cartilage, mature cartilage, and bone. Immature cartilage is produced during early stages of cartilage differentiation and can persist into adulthood, whereas mature cartilage undergoes additional stages of differentiation, including hypertrophy and mineralization. Functionally, histologically, and embryologically, these three skeletal tissues are very similar, yet unique, suggesting that one might have evolved from another. Traditional studies of the fossil record, comparative anatomy and embryology demonstrate clearly that immature cartilage evolved before mature cartilage or bone. Modern molecular approaches show that the GRNs regulating differentiation of these three skeletal cell fates are similar, yet unique, just like the functional and histological features of the tissues themselves. Intriguingly, the Sox9 GRN driving cartilage formation appears to be dominant to the Runx2 GRN of bone. Emphasizing an embryological and evolutionary transcriptomic view, we hypothesize that the Runx2 GRN underlying bone formation was co-opted from mature cartilage. We discuss how modern molecular genetic experiments, such as comparative transcriptomics, can test this hypothesis directly, meanwhile permitting levels of constraint and adaptation to be evaluated quantitatively. Therefore, comparative transcriptomics may revolutionize understanding of not only the clade-specific evolution of skeletal cells, but also the generation of evolutionary novelties, providing a modern paradigm for the evolutionary process.

No MeSH data available.


Related in: MedlinePlus

During endochondral ossification, immature cartilage, mature cartilage, and bone differentiate under the control of Sox9 and Runx2 GRNs. Chondrocytes of immature cartilage, termed resting and proliferative chondrocytes during endochondral ossification, express high levels of genes in the Sox9 GRN. Genes known to be under direct transcriptional control of Sox9 or Runx2 are highlighted in red or green text, respectively. Chondrocytes of mature cartilage, termed prehypertrophic and hypertrophic chondrocytes during endochondral ossification, express low levels of genes in the Sox9 GRN and also genes in the Runx2 GRN. Osteoblasts in perichondral and endochondral bone during endochondral ossification express genes in the Runx2 GRN. *Col1 is one of the only genes expressed in osteoblasts that is not expressed in mature chondrocytes; Col10 expression in osteoblasts is high only in some vertebrates. Col11, Decorin, and Biglycan are expressed in all three of these skeletal cell types. Similar gene expression patterns are seen in immature cartilage, mature cartilage, and bone developing in the articular surface (not shown).
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Figure 3: During endochondral ossification, immature cartilage, mature cartilage, and bone differentiate under the control of Sox9 and Runx2 GRNs. Chondrocytes of immature cartilage, termed resting and proliferative chondrocytes during endochondral ossification, express high levels of genes in the Sox9 GRN. Genes known to be under direct transcriptional control of Sox9 or Runx2 are highlighted in red or green text, respectively. Chondrocytes of mature cartilage, termed prehypertrophic and hypertrophic chondrocytes during endochondral ossification, express low levels of genes in the Sox9 GRN and also genes in the Runx2 GRN. Osteoblasts in perichondral and endochondral bone during endochondral ossification express genes in the Runx2 GRN. *Col1 is one of the only genes expressed in osteoblasts that is not expressed in mature chondrocytes; Col10 expression in osteoblasts is high only in some vertebrates. Col11, Decorin, and Biglycan are expressed in all three of these skeletal cell types. Similar gene expression patterns are seen in immature cartilage, mature cartilage, and bone developing in the articular surface (not shown).

Mentions: Skeletal histogenesis is governed by complex sets of genes, largely controlled by central transcription factors that are responsible for determining cell fate decisions (Eames et al., 2003, 2004; Kronenberg, 2003; Karsenty et al., 2009). Molecular genetic experiments demonstrate that the transcription factors Sox9 and Runx2 are the “master regulatory genes” of skeletal histogenesis. Sox9 and Runx2 expression patterns during mesenchymal condensation predict whether osteochondroprogenitor cells differentiate into immature cartilage, mature cartilage, or bone (Eames and Helms, 2004; Eames et al., 2004). Loss of Sox9 function abrogated immature and mature cartilage formation (Bi et al., 1999; Mori-Akiyama et al., 2003), whereas Runx2 loss of function blocked mature cartilage and bone formation (Hoshi et al., 1999; Inada et al., 1999; Kim et al., 1999; Enomoto et al., 2000). In gain-of-function experiments, Sox9 mis-expression induced ectopic cartilage formation, whereas Runx2 mis-expression induced ectopic mature cartilage and bone formation (Eames et al., 2004). These and other experiments show clearly that a Sox9 GRN regulates immature cartilage formation, a Runx2 GRN drives bone formation, and a combination of Sox9 and Runx2 GRNs produce mature cartilage (Figure 3). We emphasize the relevance of these transcription factors to the evolution of GRNs underlying skeletal histogenesis, since conserved, core components of GRNs (i.e., kernels) are often transcription factors (Levine and Davidson, 2005; Davidson and Erwin, 2006).


On the evolutionary relationship between chondrocytes and osteoblasts.

Gómez-Picos P, Eames BF - Front Genet (2015)

During endochondral ossification, immature cartilage, mature cartilage, and bone differentiate under the control of Sox9 and Runx2 GRNs. Chondrocytes of immature cartilage, termed resting and proliferative chondrocytes during endochondral ossification, express high levels of genes in the Sox9 GRN. Genes known to be under direct transcriptional control of Sox9 or Runx2 are highlighted in red or green text, respectively. Chondrocytes of mature cartilage, termed prehypertrophic and hypertrophic chondrocytes during endochondral ossification, express low levels of genes in the Sox9 GRN and also genes in the Runx2 GRN. Osteoblasts in perichondral and endochondral bone during endochondral ossification express genes in the Runx2 GRN. *Col1 is one of the only genes expressed in osteoblasts that is not expressed in mature chondrocytes; Col10 expression in osteoblasts is high only in some vertebrates. Col11, Decorin, and Biglycan are expressed in all three of these skeletal cell types. Similar gene expression patterns are seen in immature cartilage, mature cartilage, and bone developing in the articular surface (not shown).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
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Figure 3: During endochondral ossification, immature cartilage, mature cartilage, and bone differentiate under the control of Sox9 and Runx2 GRNs. Chondrocytes of immature cartilage, termed resting and proliferative chondrocytes during endochondral ossification, express high levels of genes in the Sox9 GRN. Genes known to be under direct transcriptional control of Sox9 or Runx2 are highlighted in red or green text, respectively. Chondrocytes of mature cartilage, termed prehypertrophic and hypertrophic chondrocytes during endochondral ossification, express low levels of genes in the Sox9 GRN and also genes in the Runx2 GRN. Osteoblasts in perichondral and endochondral bone during endochondral ossification express genes in the Runx2 GRN. *Col1 is one of the only genes expressed in osteoblasts that is not expressed in mature chondrocytes; Col10 expression in osteoblasts is high only in some vertebrates. Col11, Decorin, and Biglycan are expressed in all three of these skeletal cell types. Similar gene expression patterns are seen in immature cartilage, mature cartilage, and bone developing in the articular surface (not shown).
Mentions: Skeletal histogenesis is governed by complex sets of genes, largely controlled by central transcription factors that are responsible for determining cell fate decisions (Eames et al., 2003, 2004; Kronenberg, 2003; Karsenty et al., 2009). Molecular genetic experiments demonstrate that the transcription factors Sox9 and Runx2 are the “master regulatory genes” of skeletal histogenesis. Sox9 and Runx2 expression patterns during mesenchymal condensation predict whether osteochondroprogenitor cells differentiate into immature cartilage, mature cartilage, or bone (Eames and Helms, 2004; Eames et al., 2004). Loss of Sox9 function abrogated immature and mature cartilage formation (Bi et al., 1999; Mori-Akiyama et al., 2003), whereas Runx2 loss of function blocked mature cartilage and bone formation (Hoshi et al., 1999; Inada et al., 1999; Kim et al., 1999; Enomoto et al., 2000). In gain-of-function experiments, Sox9 mis-expression induced ectopic cartilage formation, whereas Runx2 mis-expression induced ectopic mature cartilage and bone formation (Eames et al., 2004). These and other experiments show clearly that a Sox9 GRN regulates immature cartilage formation, a Runx2 GRN drives bone formation, and a combination of Sox9 and Runx2 GRNs produce mature cartilage (Figure 3). We emphasize the relevance of these transcription factors to the evolution of GRNs underlying skeletal histogenesis, since conserved, core components of GRNs (i.e., kernels) are often transcription factors (Levine and Davidson, 2005; Davidson and Erwin, 2006).

Bottom Line: Emphasizing an embryological and evolutionary transcriptomic view, we hypothesize that the Runx2 GRN underlying bone formation was co-opted from mature cartilage.We discuss how modern molecular genetic experiments, such as comparative transcriptomics, can test this hypothesis directly, meanwhile permitting levels of constraint and adaptation to be evaluated quantitatively.Therefore, comparative transcriptomics may revolutionize understanding of not only the clade-specific evolution of skeletal cells, but also the generation of evolutionary novelties, providing a modern paradigm for the evolutionary process.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, SK Canada.

ABSTRACT
Vertebrates are the only animals that produce bone, but the molecular genetic basis for this evolutionary novelty remains obscure. Here, we synthesize information from traditional evolutionary and modern molecular genetic studies in order to generate a working hypothesis on the evolution of the gene regulatory network (GRN) underlying bone formation. Since transcription factors are often core components of GRNs (i.e., kernels), we focus our analyses on Sox9 and Runx2. Our argument centers on three skeletal tissues that comprise the majority of the vertebrate skeleton: immature cartilage, mature cartilage, and bone. Immature cartilage is produced during early stages of cartilage differentiation and can persist into adulthood, whereas mature cartilage undergoes additional stages of differentiation, including hypertrophy and mineralization. Functionally, histologically, and embryologically, these three skeletal tissues are very similar, yet unique, suggesting that one might have evolved from another. Traditional studies of the fossil record, comparative anatomy and embryology demonstrate clearly that immature cartilage evolved before mature cartilage or bone. Modern molecular approaches show that the GRNs regulating differentiation of these three skeletal cell fates are similar, yet unique, just like the functional and histological features of the tissues themselves. Intriguingly, the Sox9 GRN driving cartilage formation appears to be dominant to the Runx2 GRN of bone. Emphasizing an embryological and evolutionary transcriptomic view, we hypothesize that the Runx2 GRN underlying bone formation was co-opted from mature cartilage. We discuss how modern molecular genetic experiments, such as comparative transcriptomics, can test this hypothesis directly, meanwhile permitting levels of constraint and adaptation to be evaluated quantitatively. Therefore, comparative transcriptomics may revolutionize understanding of not only the clade-specific evolution of skeletal cells, but also the generation of evolutionary novelties, providing a modern paradigm for the evolutionary process.

No MeSH data available.


Related in: MedlinePlus