How to make a hand: a 3‐day symposium held at the University of Dundee

Abstract

Each new individual arises from a single cell which develops into an embryo. One of the most challenging problems is to determine how precise arrangements of cells and tissues are then generated in the embryo to make organs. In this issue we focus on the limb, tracing development from the initial bud to the final complex structure. Until about 10 years ago, little was known about the genetic and molecular basis of vertebrate limb development. This situation has changed dramatically, owing to the combined efforts of developmental biologists and clinical geneticists. Now that we know many of the genes that are required to make a limb, we are beginning to understand how anatomy is generated from the genetic information. This issue of the Journal of Anatomy consists mainly of reviews written by speakers at the ‘How to make a hand’ symposium. We start by considering how limb pattern is specified in the earliest stages of development (Panman & Zeller; Hill et al.) as revealed by powerful genetic studies in mice. Both papers address issues concerning Sonic hedgehog, one of the key genes in establishing the anatomy of the hand. Another gene in the same family, Indian Hedgehog, appears to be responsible for the polydactylous phenotype of a mouse mutant (Crick et al.). The importance of mouse models as informative models for understanding human development is illustrated by the fact that genes employed at these crucial early stages, including Sonic hedgehog, have been found to underlie human conditions in which there are marked anatomical abnormalities of the limb. This topic is considered in more detail by Wilkie, while Miedzybrodzka provides a clinical perspective on one of most common limb abnormalities, clubfoot. One of the crucial issues is how pattern information is translated into tissue organization. Lonai considers the involvement of extracellular matrix in epithelial–mesenchymal interactions in early stages of limb development. Early events establish the organization that leads to the complex anatomy of the vertebrate limb, with precise arrangements of several types of differentiated cells and tissues including cartilage, bone, tendon and muscle. The early skeleton is laid down in cartilage, and Sanz-Ezquerro & Tickle discuss skeletal morphogenesis of the digits with particular reference to experimental work in chick embryos. Buckingham et al. and Francis-West et al. review how limb musculature is established, including the origin of myogenic cells in the somites and muscle differentiation. These two studies, focused on observations in mouse and chick, respectively, together show how studies on different vertebrates are complementary and give added value. In the two research articles published in this issue, Martin & Mackay describe the specialized control of timing of limb development in the opposum Monodelphis; Oldfield & Evans cover tendon development. The limb is supplied with nerves and blood vessels. Turney et al. describe a new chick model for investigating mechanisms involved in limb innnervation. Vargesson addresses the genetic basis of vascularization, concentrating on the importance of TGF beta signalling, while Adams deals with the genes that are now known to be responsible for specifying arteries vs. veins. Finally, the limb must also be covered by skin that acts as a barrier between the internal and external environments, and, importantly in the hand (and foot!), becomes regionally specialized. Byrne et al. provide a detailed review of how the skin develops its barrier function, while Porter reviews the development of hairs, one of the main types of skin appendage. Inherited defects can affect the skin and even be restricted to just the skin on the hands; these are reviewed by McLean. The issue ends with a hypothesis about how the human hand may have evolved for throwing (Young). The February issue of Journal of Anatomy will contain two other review articles from the symposium that address methodology: Sharpe will highlight the possibilities of a new imaging method that could be applied to the developing limb, while Boyde discusses a method of looking at bone architecture.