(A) About 380 million years ago, lobe-finned tetrapods were still water-bound (top). Yet, lengthwise cross sections of their forelimb bones (bottom) show that they had already evolved limbs that elongate through calcified cartilage columns (dark blue) within the metaphysis – the area near the extremities of the bones that features a ‘growth plate’ formed of cartilage (light blue). Marrow processes — the blood vessels (red) between the mineralized columns in the growth plate — were also present at this stage. However they did not communicate freely with the open cavity inside the shaft. (B) Tetrapods that first ventured onto land 360 million years ago (top) also elongated their limbs at the growth plate. Their bones do show evidence of marrow processes occurring within the metaphysis (bottom), but they still produce red blood cells via their liver and kidney. Indeed, a trait necessary for red blood cell production in the bone is missing: the blood vessels of the marrow processes open into small connected cavities in the bone rather than communicating with the open marrow cavity. (C) Fully terrestrial tetrapods appeared 300 million years ago (top), and they retained the fan-like growth plate of their ancestors (bottom). However, the cavities within their bones indicate that the marrow processes were interconnected via blood vessels, and that they communicated with the bone marrow. This suggests that red blood cells were now produced within bone.