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Review
. 2024 Jul 3;12(3):18.
doi: 10.3390/jdb12030018.

Getting to the Core: Exploring the Embryonic Development from Notochord to Nucleus Pulposus

Luca Ambrosio  1   2   3 , Jordy Schol  3 , Clara Ruiz-Fernández  3 , Shota Tamagawa  4 , Kieran Joyce  5   6 , Akira Nomura  3 , Elisabetta de Rinaldis  2 , Daisuke Sakai  3 , Rocco Papalia  1   2 , Gianluca Vadalà  1   2 , Vincenzo Denaro  1
Affiliations
Review

Getting to the Core: Exploring the Embryonic Development from Notochord to Nucleus Pulposus

Luca Ambrosio et al. J Dev Biol. .

Abstract

The intervertebral disc (IVD) is the largest avascular organ of the human body and plays a fundamental role in providing the spine with its unique structural and biomechanical functions. The inner part of the IVD contains the nucleus pulposus (NP), a gel-like tissue characterized by a high content of type II collagen and proteoglycans, which is crucial for the disc's load-bearing and shock-absorbing properties. With aging and IVD degeneration (IDD), the NP gradually loses its physiological characteristics, leading to low back pain and additional sequelae. In contrast to surrounding spinal tissues, the NP presents a distinctive embryonic development since it directly derives from the notochord. This review aims to explore the embryology of the NP, emphasizing the pivotal roles of key transcription factors, which guide the differentiation and maintenance of the NP cellular components from the notochord and surrounding sclerotome. Through an understanding of NP development, we sought to investigate the implications of the critical developmental aspects in IVD-related pathologies, such as IDD and the rare malignant chordomas. Moreover, this review discusses the therapeutic strategies targeting these pathways, including the novel regenerative approaches leveraging insights from NP development and embryology to potentially guide future treatments.

Keywords: degeneration; development; embryology; intervertebral disc; notochordal cells; nucleus pulposus; regenerative medicine; transcription factors.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic representation of the juvenile healthy IVD (left) and microscopic structure of the NP. Abbreviations: IVD = intervertebral disc; NP = nucleus pulposus. Created with BioRender.com.
Figure 2
Figure 2
Murine NC cluster appearance following NP aspiration under microscopic observation (A). After plastic adherence (B), NCs display a characteristic vacuolated morphology (red arrow). Abbreviations: NC = notochordal cell; NP = nucleus pulposus. Scale bars = 50 μm.
Figure 3
Figure 3
Schematic representation of the developmental stages of the NP and annotation of the transcription factors speculated to be involved. Abbreviation: E = embryonic day, NP = nucleus pulposus, and w = embryonic week. Colored text matches the tissues illustrated with identical colors. Created with Adobe Illustrator.
Figure 4
Figure 4
Schematic representation of IDD (left) and microscopic structure of the degenerative NP. Abbreviations: AF = annulus fibrosus; ECM = extracellular matrix; IDD = intervertebral disc degeneration; NP = nucleus pulposus; NPC = nucleus pulposus cells. ROS = reactive oxygen species. Created with BioRender.com.
See this image and copyright information in PMC

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