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Embryologically, the appendicular skeleton arises from mesenchyme, a type of embryonic tissue that can differentiate into many types of tissues, including bone or muscle tissue. Mesenchyme gives rise to the bones of the upper and lower limbs, as well as to the pectoral and pelvic girdles. Development of the limbs begins near the end of the fourth embryonic week, with the upper limbs appearing first. Thereafter, the development of the upper and lower limbs follows similar patterns, with the lower limbs lagging behind the upper limbs by a few days.
Each upper and lower limb initially develops as a small bulge called a limb bud , which appears on the lateral side of the early embryo. The upper limb bud appears near the end of the fourth week of development, with the lower limb bud appearing shortly after ( [link] ).
Initially, the limb buds consist of a core of mesenchyme covered by a layer of ectoderm. The ectoderm at the end of the limb bud thickens to form a narrow crest called the apical ectodermal ridge . This ridge stimulates the underlying mesenchyme to rapidly proliferate, producing the outgrowth of the developing limb. As the limb bud elongates, cells located farther from the apical ectodermal ridge slow their rates of cell division and begin to differentiate. In this way, the limb develops along a proximal-to-distal axis.
During the sixth week of development, the distal ends of the upper and lower limb buds expand and flatten into a paddle shape. This region will become the hand or foot. The wrist or ankle areas then appear as a constriction that develops at the base of the paddle. Shortly after this, a second constriction on the limb bud appears at the future site of the elbow or knee. Within the paddle, areas of tissue undergo cell death, producing separations between the growing fingers and toes. Also during the sixth week of development, mesenchyme within the limb buds begins to differentiate into hyaline cartilage that will form models of the future limb bones.
The early outgrowth of the upper and lower limb buds initially has the limbs positioned so that the regions that will become the palm of the hand or the bottom of the foot are facing medially toward the body, with the future thumb or big toe both oriented toward the head. During the seventh week of development, the upper limb rotates laterally by 90 degrees, so that the palm of the hand faces anteriorly and the thumb points laterally. In contrast, the lower limb undergoes a 90-degree medial rotation, thus bringing the big toe to the medial side of the foot.
Watch this animation to follow the development and growth of the upper and lower limb buds. On what days of embryonic development do these events occur: (a) first appearance of the upper limb bud (limb ridge); (b) the flattening of the distal limb to form the handplate or footplate; and (c) the beginning of limb rotation?
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