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• W2563668803 abstract "Pax1 and Pax9 play redundant, synergistic functions in the patterning and differentiation of the sclerotomal cells that give rise to the vertebral bodies and intervertebral discs (IVD) of the axial skeleton. They are conserved in mice and humans, whereby mutations/deficiency of human PAX1/PAX9 have been associated with kyphoscoliosis. By combining cell-type specific transcriptome and ChIP-sequencing data, we identified the roles of Pax1/Pax9 in cell proliferation, cartilage development and collagen fibrillogenesis, which are vital in early IVD morphogenesis. Pax1 is up-regulated in the absence of Pax9, while Pax9 is unaffected by the loss of Pax1/Pax9. We identified the targets compensated by a single- or double-copy of Pax9. They positively regulate many of the cartilage genes known to be regulated by Sox5/Sox6/Sox9 and are connected to Sox5/Sox6 by a negative feedback loop. Pax1/Pax9 are intertwined with BMP and TGF-B pathways and we propose they initiate expression of chondrogenic genes during early IVD differentiation and subsequently become restricted to the outer annulus by the negative feedback mechanism. Our findings highlight how early IVD development is regulated spatio-temporally and have implications for understanding kyphoscoliosis." @default.
• W2563668803 created "2017-01-06" @default.
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• W2563668803 date "2016-01-01" @default.
• W2563668803 modified "2023-10-17" @default.
• W2563668803 title "A developmental transcriptomic analysis of<i>Pax1</i>and<i>Pax9</i>in embryonic intervertebral disc development" @default.
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• W2563668803 doi "https://doi.org/10.1242/bio.023218" @default.
• W2563668803 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5312110" @default.
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