Nell-1 promotes chondrogenic differentiation and maturation of ex vivo cultured Runx2−/− E14.5 hind limbs. Hind limb explants were isolated from WT and Runx2−/− E14.5 mouse embryos, cultured in media with or without 2.0 μg/mL Nell-1 protein for 5 days, fixed in 4% paraformaldehyde, divided into sections, and stained with hematoxylin and eosin (H&E) for histological evaluation and immunohistochemistry of collagen II and collagen X to assess chondrogenic differentiation and maturation. Boxed areas are shown at higher magnification below. Scale bars = 100 μm. PBS, phosphate-buffered saline; WT, wild-type.