Vertebrate Limb Development

Abstract

The vertebrate limb develops from a small bud of mesoderm cells encased in ectoderm. The molecules involved in the determination of limb mesoderm and formation of the bud include Hox genes, T-box transcription factors, WNTs and FGFs. The limb bud is equipped with signaling regions that control outgrowth and pattern formation along the three main axes of the limb- the proximo-distal, dorso-ventral and antero-posterior axes. The apical ectodermal ridge at the tip of the bud controls proximo-distal outgrowth which is accompanied by the sequential formation of the structures along this axis; the ectoderm covering the sides of the limb bud controls dorso-ventral pattern formation; and the polarizing region, a small region of mesoderm cells at one side of the bud, controls antero-posterior pattern formation of the distal limb. The signals involved include FGFs (from the apical ectodermal ridge), WNTs (from dorsal ectoderm) and SHH (from the polarizing region) and these signals interact so that pattern formation is co-ordinated along all three axes of the limb. Pattern formation generates the complex limb anatomy and the final form of the limb is produced by morphogenesis and growth. Most of the knowledge of how vertebrate limbs develop comes from experiments on chick and mouse embryos. The identification of the genes involved in limb development in these model organisms provides direct links to clinical genetics and also begins to give insights into the evolution of the morphological diversity of limbs between vertebrate species.