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Owing to the lack of understanding of the cellular mechanisms involved in IVDD formation effective treatment options are still unavailable. Primary cilia are microtubule\u2010based organelles that play important roles in the organ development. Intraflagellar transport (IFT) proteins are essential for the assembly and bidirectional transport within the cilium. Role of cilia and IFT80 protein in intervertebral disc (IVD) development, maintenance, and degeneration are largely unknown. Using cilia\u2010GFP mice, we found presence of cilia on growth plate (GP), cartilage endplate (EP) annulus fibrosus (AF), and nucleus pulposus (NP) with varying ciliary length. Cilia length in NP and AF during IVDD were significantly decreased. However, cilia numbers increased by 63% in AF during repair. Deletion of IFT80 in type II collagen\u2010positive cells resulted in cilia loss in GP and EP, and disrupted IVD structure with disorganized and decreased GP, EP, and internal AF (IAF), and less compact and markedly decreased gel\u2010like matrix in the NP. Deletion of IFT80 in type I collagen\u2010positive cells led to a disorganized outer AF (OAF) with thinner, loosened, and disconnected fiber alignment. Mechanistic analyses showed that loss of IFT80 caused a significant increase in cell apoptosis in the IVD, and a marked decrease in expression of chondrogenic markers \u2010 type II collagen, sox9, aggrecan, and hedgehog (Hh) signaling components, including Gli1 and Patch1 in the IVD of IFT80\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    ; Col2\u2010creERT mice, and Gli1 and Patch1 expression in the OAF of IFT80\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    ; Col1\u2010creERT mice. Interestingly, Smoothened agonist\u2010SAG rescued OAF cell proliferation and osteogenic differentiation. Our findings demonstrate that ciliary IFT80 is important for the maintenance of IVD cell organization and function through regulating the cell survival and Hh signaling.\n                  <\/jats:p>","DOI":"10.1096\/fj.201902838r","type":"journal-article","created":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T03:04:57Z","timestamp":1585537497000},"page":"6741-6756","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Ciliary IFT80 is essential for intervertebral disc development and maintenance"],"prefix":"10.1096","volume":"34","author":[{"given":"Xinhua","family":"Li","sequence":"first","affiliation":[{"name":"Department of Basic and Translational Science School of Dental Medicine University of Pennsylvania Philadelphia PA USA"},{"name":"Department of Spinal Surgery East Hospital Tongji University School of Medicine Shanghai 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