2 Developmental Patterning of the Limb Skeleton

Abstract

The vertebrate skeleton is composed of approximately 200 bones, ranging in shape and size from the delicate bones of the mammalian inner ear to the robust femur. Each individual bone forms in a precise location and orientation with respect to its neighbors and in relation to force generating and transmitting tissues—the muscles, tendons, and ligaments. The appropriate structure of the bones is essential for function of the skeleton to support and move the body, and depends on an array of molecular cues that pattern their formation early in development. Our knowledge of developmental mechanism patterning all tissues and organs of the body, including the skeleton, is largely derived from experiments using two model systems—chick and mouse embryos. While aspects of patterning the craniofacial and axial skeletal elements have been elucidated, development of the bones of the limbs is particularly well understood. The limbs are easily accessible for embryological manipulation and are expendable for the survival of prenatal animals, allowing for analysis of late developmental phenotypes after genetic or surgical perturbation. The developing limb bud has therefore become an important model for the investigation of cellular and molecular mechanisms that pattern the tissues that give rise to bones. The tetrapod limb is of additional interest from an evolutionary perspective because it is a conserved but malleable structure whose adaptive variations in form increase an animal’s fitness in different ecological niches—by promoting mobility, aiding in the acquisition of food, fighting against or escaping from predators, and assisting in reproduction...