{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T20:19:41Z","timestamp":1787343581221,"version":"build-2736575974"},"reference-count":154,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T00:00:00Z","timestamp":1719964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JDB"],"abstract":"<jats:p>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\u2019s 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.<\/jats:p>","DOI":"10.3390\/jdb12030018","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T08:45:34Z","timestamp":1719996334000},"page":"18","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Getting to the Core: Exploring the Embryonic Development from Notochord to Nucleus Pulposus"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2424-1274","authenticated-orcid":false,"given":"Luca","family":"Ambrosio","sequence":"first","affiliation":[{"name":"Operative Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Research Unit of Orthopaedic and Trauma Surgery, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, 01128 Rome, Italy"},{"name":"Department of Orthopaedic Surgery, Tokai University School of Medicine, Isehara 259-1143, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5489-2591","authenticated-orcid":false,"given":"Jordy","family":"Schol","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Tokai University School of Medicine, Isehara 259-1143, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7959-9826","authenticated-orcid":false,"given":"Clara","family":"Ruiz-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Tokai University School of Medicine, Isehara 259-1143, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5384-8158","authenticated-orcid":false,"given":"Shota","family":"Tamagawa","sequence":"additional","affiliation":[{"name":"Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kieran","family":"Joyce","sequence":"additional","affiliation":[{"name":"C\u00daRAM, SFI Research Centre for Medical Devices, University of Galway, H91 W2TY Galway, Ireland"},{"name":"School of Medicine, University of Galway, H91 W2TY Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8627-0620","authenticated-orcid":false,"given":"Akira","family":"Nomura","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Tokai University School of Medicine, Isehara 259-1143, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"de Rinaldis","sequence":"additional","affiliation":[{"name":"Research Unit of Orthopaedic and Trauma Surgery, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, 01128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Tokai University School of Medicine, Isehara 259-1143, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocco","family":"Papalia","sequence":"additional","affiliation":[{"name":"Operative Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Research Unit of Orthopaedic and Trauma Surgery, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, 01128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Vadal\u00e0","sequence":"additional","affiliation":[{"name":"Operative Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Research Unit of Orthopaedic and Trauma Surgery, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, 01128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Denaro","sequence":"additional","affiliation":[{"name":"Operative Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1002\/jor.23195","article-title":"Molecular mechanisms of biological aging in intervertebral discs","volume":"34","author":"Vo","year":"2016","journal-title":"J. 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