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. Author manuscript; available in PMC: 2018 Mar 30.
Published in final edited form as: Wiley Interdiscip Rev Dev Biol. 2016 Sep 1;6(1):10.1002/wdev.245. doi: 10.1002/wdev.245

FIGURE 6.

FIGURE 6

Chondrocyte fate decisions. (a) Section of the knee joint from an 8-week-old mouse shows that Col2a1 expression (green) is stronger in growth plate chondrocytes (arrowhead) compared to articular chondrocytes (arrow). Superficial joint chondrocytes are labeled by treatment of Prg4-CreER; Rosa26:memTomato/memGFP mice with Tamoxifen three weeks earlier (anti-GFP antibody staining detects Prg4-CreER-converted cells in red). (c) Compared to the complex mammalian knee joint, the hyoid joint of 6-day-old zebrafish (arrows) provides a simplified model for understanding the specification of joint chondrocyte fate. In this example, transient chondrocytes express both a sox10:dsRed transgene (red) and a col2a1a:GFP transgene (green). In contrast, joint chondrocytes express sox10 but much lower levels of col2a1a, suggesting they are immature. (c) Cells within a mesenchymal condensation initially express Barx1 and then go on to express Sox9 (and in zebrafish also the related SoxE family member sox10), Dcx, and low levels of Col2a1 (in particular an A splice isoform). In the growth plate, these cells mature into prehypertrophic chondrocytes that express high levels of Col2a1 and Matn1 and then hypertrophic chondrocytes that express Col10a1, Runx2, and other genes associated with mineralization. In contrast, interzone cells differentiate into articular chondrocytes that maintain low Col2a1 and instead express Gdf5 and later Prg4. Although Wnt9a and Fgf18 promote a joint fate, Ihh signaling controls cartilage maturation. Specification of articular chondrocyte fate is promoted through inhibition of cartilage maturation by a number of transcription factors and chromatin remodelers, including Iroquois proteins (Irx), Trps1, Nkx3.2, Cux1, Erg, Lrf, and Hdac1. (d) Under the control of signaling factors including Gdf5/6, Wnt9a, Fgf18, TGFβ and Noggin, chondroprogenitor cells mature to form the different chondrocyte layers of the growth plate (darker blue) or remain relatively immature within the joint (orange cells in light blue matrix). Factors including Trps1, Has, and Ihh then drive interzone cells to cavitate as superficial zone articular chondrocytes (brown) begin to produce lubricating molecules such as Prg4.