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Fig. 9. Model of the role of C4st1 during cartilage development. The organized growth plate of wild-type cartilage contains proliferating (p), columnar (c) and hypertrophic (h) chondrocytes (grey) surrounded by ECM containing CS (orange). C4st1^gt/gt-mutant growth plates are severely reduced in length, but display increased width. The chondrocyte layers are disorganized and chondrocyte columns are not oriented along the longitudinal axis of the bone. CS (orange) is mostly absent from the ECM and instead is located in the pericellular space surrounding chondrocytes. There is a dramatic increase in the thickness of the bone collar (dark grey) in mutant growth plates and bone. Whereas Ihh signaling to proliferating chondrocytes is not significantly altered in mutant growth plates (red arrows), BMP signaling to both proliferating and hypertrophic chondrocytes is reduced (yellow arrows), and TGFß signaling to proliferating and hypertrophic chondrocytes (blue arrows) is dramatically increased in mutant growth plates. Imbalance in apoptotic signals leads to a dramatic increase in the area prone to undergo apoptosis (indicated by black brackets).

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