Developmental mechanisms of intervertebral disc and vertebral column formation

Abstract

The vertebral column consists of repeating units of ossified vertebrae that are adjoined by fibrocartilagenous intervertebral discs. These structures form from the embryonic notochord and somitic mesoderm. In humans, congenital malformations of the vertebral column include scoliosis, kyphosis, spina bifida, and Klippel Feil syndrome. In adulthood, a common malady affecting the vertebral column includes disc degeneration and associated back pain. Indeed, recent reports estimate that low back pain is the number one cause of disability worldwide. Our review provides an overview of the molecular mechanisms underlying vertebral column morphogenesis and intervertebral disc development and maintenance, with an emphasis on what has been gleaned from recent genetic studies in mice. The aim of this review is to provide a developmental framework through which vertebral column formation can be understood so that ultimately, research scientists and clinicians alike can restore disc health with appropriately designed gene and cell-based therapies. WIREs Dev Biol 2017, 6:e283. doi: 10.1002/wdev.283 For further resources related to this article, please visit the WIREs website.

The Immune Privilege of the Intervertebral Disc: Implications for Intervertebral Disc Degeneration Treatment

“…The AF is composed of 15-25 concentric layers, which consists of alternatingly aligned oblique collagen fibers interspersed with proteoglycans. This feature holds the NP by confine its swelling pressure and resisting shear and tensile stresses from the internal pressure exerted by the NP [12]. The CEP is a layer of cartilage with about 0.5-1 mm thickness.…”

“…On the other hand, the surrounding dense ring of sclerotome-derived connective tissue develops to the AF with abundant ECM containing collagens and glycoproteins. Meanwhile, chondrocyte differentiation and endochondral bone formation occur in the vertebral bodies with high concentrations of bone morphogenetic protein (BMP) activity [12]. When the bony vertebra is formed, hyaline cartilage adjacent to the IVD is maintained and develops to the CEP at the end plate ( Figure 1).…”

TGF-β signaling in intervertebral disc health and disease

“…The IVD develops from cells contained in both the sclerotome and notochord 26 . The notochord derived from the axial mesoderm forms the NP, and the sclerotome derived from somite gives rise to the AF and CEP 27,28 .…”

NOTO Transcription Factor Directs Human Induced Pluripotent Stem Cell-Derived Mesendoderm Progenitors to a Notochordal Fate

“…Through secretion of SHH and NOGGIN, the notochord induces the migration and differentiation of the somite-derived sclerotomal cells to form the spine with alternating vertebrae and annulus fibrosus (IVD fibrous peripheral part). During organogenesis, NC accumulate and persist solely in the presumptive intervertebral region to form the NP [17,18].…”