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In particular, developing limbs can be readily manipulated (both surgically and genetically) without influencing the viability of the embryo, yet many of the emerging principles can be applied to under- standing earlier developmental events, such as specify- ing the main body axes. To set the scene we start with a brief overview of limb development as it was understood before the use of the tools of molecular biology. Then we follow with an assess- ment of where we stand today and conclude with a dis- cussion of what we might hope to learn in the near future. The past: limb organizer centres Limb specification begins very early during develop- ment with the establishment of a special group of cells termed the ‘limb field’ 1 . As development proceeds, pre- cisely positioned limb buds appear, opposite each other, as a result of the coordinated proliferation of cells derived from the somites and the lateral plate meso- derm (Fig. 1a–c) 2,3 . Although the mechanisms that ini- tially establish and position the limb field are still unknown, nearly five decades of transplantation experi- ments have provided extraordinary insights into the subsequent development of the limb bud. It is now clear that very early interactions between cells ensure that the limb develops with predetermined anteroposterior and dorsoventral asymmetry. These signals are (Fig. 1d, e): (1) the ectodermal cells 4,5 covering the limb bud that, at early stages, con- trol the dorsoventral asymmetry of the future limb; (2) a specialized epithelium, located at the tip of the growing limb bud, termed the apical ectodermal ridge (AER) 6–8 that, in conjunction with the cells directly underneath, (3) the so-called progress zone (PZ) 9 , directs the out- growth of the limb along the proximodistal axis; and (4) a group of mesodermal cells located at the posterior margin of the limb bud, termed the zone of polarizing activity (ZPA) 10 or polarizing region, that controls the outgrowth of the limb along the anteroposterior axis. The present: the molecular basis of limb development The advent of molecular and genetic techniques has not only allowed us to begin to unravel how these organ- izer centres interact with each other, but has also led to the identification of some of the molecules directly responsible for providing the initial positional cues that establish these signalling centres. These molecules have been identified through a variety of means: differential screening; chance; purely biochemical approaches; or by homology to developmental genes in Drosophila where they were identified in mutation screens. A brief examination of the character of these genes reveals that they encode two types of protein: transcriptional regu- lators and signalling proteins. Limbs are moving: where are they going? JOHN W.R. SCHWABE (jws2@mrc-lmb.cam.ac.uk) CONCEPCIÓN RODRIGUEZ- ESTEBAN (crodriguez@aim.salk.edu) JUAN CARLOS IZPISÚA BELMONTE (belmonte@salk.edu) The past decade has witnessed many changes in the way in which biologists study vertebrate development. Like curious children, we have progressed from merely watching and playing with our toys to the more exciting activity of taking them apart. This progression is mainly due to the application of a number of new techniques that allow us not only to ablate gene function, but also to induce gene activity inappropriately in time and space. Through the use of these techniques we can now disassemble our ‘toys’ and begin to understand how the pieces fit together and, thus, we are beginning to understand how the vertebrate embryo develops. Additionally, the analysis and comparison of limb development in diverse species has provided much insight into the evolutionary mechanisms through which changes in developmental pathways have led to the extraordinary diversity of limbs.