Development of the Intervertebral Disc

Cox, Megan K.; Serra, Rosa

doi:10.1007/978-3-7091-1535-0_3

Cited by 11 publications

(21 citation statements)

References 169 publications

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“…In the fossil record, however, we see that generalised centrum morphology does not indicate ball-and-socket joints 1 with hyaline cartilage. This agrees with higher-level amniote phylogeny that reveals the basal condition of vertebral morphology to be an amphicoelous vertebral centrum with a notochordal canal 1,10 , as already seen in the amniote sistergroup, Diadectomorpha 1 (Fig. 2).…”

supporting

confidence: 89%

“…This has created confusion because in these same studies, it is stated or illustrated that the avian 'IVD' lacks a NP and is not homologous to the IVD proper. Given the complex distribution of the different types of intervertebral joints on the amniote tree, further studies on well-preserved fossils in combination with soft tissue histology of extant taxa and developmental studies hold great potential 10 . The evolutionary scenario presented here results in hypotheses that are testable using classical embryology and developmental genetics.…”

Section: Discussionmentioning

confidence: 99%

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Palaeontological evidence reveals convergent evolution of intervertebral joint types in amniotes

Scaal

Schellhorn

Kogan

et al. 2020

Sci Rep

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the intervertebral disc (iVD) has long been considered unique to mammals. palaeohistological sampling of 17 mostly extinct clades across the amniote tree revealed preservation of different intervertebral soft tissue types (cartilage, probable notochord) seen in extant reptiles. The distribution of the fossilised tissues allowed us to infer the soft part anatomy of the joint. Surprisingly, we also found evidence for an IVD in fossil reptiles, including non-avian dinosaurs, ichthyosaurs, plesiosaurs, and marine crocodiles. Based on the fossil dataset, we traced the evolution of the amniote intervertebral joint through ancestral character state reconstruction. The IVD evolved at least twice, in mammals and in extinct diapsid reptiles. From this reptilian IVD, extant reptile groups and some non-avian dinosaurs independently evolved a synovial ball-and-socket joint. The unique birds dorsal intervertebral joint evolved from this dinosaur joint. The tuatara and some geckos reverted to the ancestral persisting notochord. Morphology of the vertebral column has provided zoologists with key anatomical characters for groups of amniotes 1. This includes the intervertebral disc (IVD), a soft tissue feature, which has been considered to be unique to mammals 2-4. However, although the importance of soft tissue analysis in fossils is clearly recognised today 5-7 , investigations on soft tissue in the vertebral column, namely of joints and intervertebral spaces, have not been done 5. Neither has the evolution of the intervertebral joint been reconstructed using phylogenetic methods such as ancestral state reconstruction (ASR) 8. The intervertebral disc (IVD) is a fibrocartilaginous synarthrotic joint connecting the vertebral centra of mammals. It provides intervertebral flexibility, allowing for a wide range of movements and is involved in shock absorbance and transmission of mechanical forces 9,10. The IVD is thus of eminent biomechanical and clinical importance in the human vertebral column and has been studied from multiple perspectives in biological, medical and veterinary science 11-13. The crucial function of the IVD is to withstand forces acting on the axial skeleton, and gradual failure of IVD function from degenerative processes often leads to pathological symptoms 14. The mammalian IVD is composed of two distinct parts, the nucleus pulposus (NP) and the annulus fibrosus (AF). The NP is the hydrophilic proteoglycan-rich gelatinous core of the IVD. Surrounding the NP is the AF, a lamellate ring of spirally arranged layers of collagen I and fibrocartilage. The joint formed by the IVD is further stabilized by intervertebral ligaments that insert in the periosteal cortex of the adjacent vertebral centra. Due to the lack of soft tissue preservation in fossils, however, the evolutionary origins of the IVD among Amniota (true land animals) have been poorly understood 10. As increasing numbers of fossil amniote specimens

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supporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Palaeontological evidence reveals convergent evolution of intervertebral joint types in amniotes

Scaal

Schellhorn

Kogan

et al. 2020

Sci Rep

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“…Intervertebral disc (IVD) are derived from embryonic structures called the sclerotome and notochord [1–3]. The nucleus pulposus, the cushioning core of the mature IVD, is derived from the notochord while the annulus fibrosus (AF), which provides the structural properties of the IVD, is derived from sclerotome.…”

Section: Introductionmentioning

confidence: 99%

Erg cooperates with TGF-β to control mesenchymal differentiation

Cox

Appelboom

Ban

et al. 2014

Experimental Cell Research

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Transforming growth factor β (TGF-β) signaling plays an integral role in skeletal development. Conditional deletion of the TGF-β type II receptor (Tgfbr2) from Type II Collagen (Col2a) expressing cells results in defects in development of the annulus fibrosus (AF) of the intervertebral disc (IVD). We previously used microarray analysis to search for marker genes of AF as well as transcription factors regulated by TGF-β during AF development. The transcription factor avian erythroblastosis virus E-26 (v-ets) oncogene related (Erg) was identified in the microarray screen as a candidate regulator of AF development. To study the effects of TGF-β on AF differentiation and the role of Erg in this process, we used mouse sclerotome grown in micromass cultures. At 0.5 ng TGF-β/ml, sclerotome cells started to express markers of AF. Regulation of Erg by TGF-β was confirmed in these cells. In addition, TGF-β soaked Affi-gel beads implanted into the axial skeleton of stage HH 25 chick embryos showed that TGF-β could induce expression of Erg mRNA in vivo. Next, an adenovirus to over-express Erg in primary sclerotome micromass cultures was generated. Over-expression of Erg led to a change in cell morphology and inhibition of differentiation into hyaline cartilage as seen by reduced Alcian blue staining and decreased Sox9 and c-Maf expression. Erg was not sufficient to induce expression of AF markers and expression of Sca1, a marker of pluripotent progenitor cells, was upregulated in Erg expressing cells. When cells that ectopically expressed Erg were treated with TGF-β, enhanced expression of specific differentiation markers was observed suggesting Erg can cooperate with TGF-β to regulate differentiation of the sclerotome. Furthermore, we showed using co-immunopreciptiation that Erg and Smad3 bind to each other suggesting a mechanism for their functional interaction.

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“…The IVD consists of two primary regions, the nucleus pulposus (NP) and the annulus fibrosus (AF) . The NP is derived from the notochord and the AF is derived from sclerotome . The NP and AF are composed of collagens and proteoglycans, such as collagens I and II and aggrecan with the NP having very high proteoglycan and water content relative to the AF .…”

Section: Introductionmentioning

confidence: 99%

“…[8][9][10] The NP is derived from the notochord and the AF is derived from sclerotome. 11 The NP and AF are composed of collagens and proteoglycans, such as collagens I and II and aggrecan with the NP having very high proteoglycan and water content relative to the AF. [8][9][10] The mouse sternum also has a fibrocartilage joint in between each sternebrae, where the sternum and ribs connect called the sternocostal joint (SJ).…”

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confidence: 99%

Tgfbr2 is required in Acan‐expressing cells for maintenance of the intervertebral and sternocostal joints

2018

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Background Members of the transforming growth factor beta (TGF‐β) family are secreted proteins that regulate skeletal development. TGF‐β signaling is critical in embryonic development of the annulus fibrosus (AF) of the intervertebral disc (IVD). To address the question of the role of TGF‐β signaling in postnatal development and maintenance of the skeleton, we generated mice in which Tgfbr2 was deleted at 2‐weeks of age in Aggrecan (Acan)‐expressing cells using inducible Cre/LoxP recombination. Methods Localization of Cre recombination was visualized by crossing Acan tm1(cre/ERT2)Crm mice to fluorescent mTmG reporter mice. Acan tm1(cre/ERT2)Crm mice were mated to Tgfbr2 LoxP/LoxP mice and Cre recombinase was activated by tamoxifen injection at 2‐weeks postnatally. Following tamoxifen injection, mice were aged to 3, 6, and 12‐months and control mice were compared to the experimental (cKO) group. Mice were initially analyzed using X‐ray and skeletal preparations. Sternocostal joints and IVD tissues were further analyzed histologically by hematoxylin and eosin (H&E), Safranin O, and Picrosirius Red staining as well as Col10 immunostaining. Results Cre recombination was observed in the IVD and sternocostal joints. X‐ray analysis revealed osteophyte formation within the disc space of 12‐month‐old cKO mice. Skeletal preparations confirmed calcification within the IVD and the sternocostal joints in cKO mice. H&E staining of cKO IVD revealed disorganized growth plates, delay in the formation of the bony endplate, and Col10 staining in the AF indicative of ectopic endochondral bone formation. Furthermore, proteoglycan loss was observed and collagen bundles within the inner AF were thinner and less organized. Alterations in the IVD were apparent beginning at 3 months and were progressively more visible at 6 and 12 months. Similarly, histological analysis of cKO sternocostal joints revealed joint calcification, proteoglycan loss, and disorganization of the collagen architecture at 12 months of age. Conclusions TGF‐β signaling is important for postnatal development and maintenance of fibrocartilaginous IVD and sternocostal joints.

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Development of the Intervertebral Disc

Cited by 11 publications

References 169 publications

Palaeontological evidence reveals convergent evolution of intervertebral joint types in amniotes

Palaeontological evidence reveals convergent evolution of intervertebral joint types in amniotes

Erg cooperates with TGF-β to control mesenchymal differentiation

Tgfbr2 is required in Acan‐expressing cells for maintenance of the intervertebral and sternocostal joints

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