A developmental transcriptomic analysis of and in embryonic intervertebral disc development.

and 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 mutation/deficiency of human has been associated with kyphoscoliosis. By combining cell-type-specific transcriptome and ChIP-sequencing data, we identified the roles of / in cell proliferation, cartilage development and collagen fibrillogenesis, which are vital in early IVD morphogenesis. is up-regulated in the absence of , while is unaffected by the loss of We identified the targets compensated by a single- or double-copy of They positively regulate many of the cartilage genes known to be regulated by S and are connected to by a negative feedback loop. 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.