The gene encoding the secreted protein Sonic hedgehog (Shh) is expressed in the polarizing region (or zone of polarizing activity), a small group of mesenchyme cells at the posterior margin of the vertebrate limb bud. Detailed analyses have revealed that Shh has the properties of the long sought after polarizing region morphogen that specifies positional values across the antero-posterior axis ...

The vertebrate limb is one of the most relevant experimental models in which to analyse cell-cell signalling during patterning of embryonic fields and organogenesis. Recently, the combination of molecular and genetic studies with experimental manipulation of developing limb buds has significantly advanced our understanding of the complex molecular interactions coordinating limb bud outgrowth an...

Sonic hedgehog (Shh) expression in the developing limb is associated with the zone of polarising activity (ZPA), and both are restricted to the posterior part of the limb bud. We show that the expression patterns of Shh and Gli3, a member of the Gli-family believed to function in transcriptional control, appear to be mutually exclusive in limb buds of mouse embryos. In the polydactyly mouse mut...

Mice homozygous for the recessive limb deformity (ld) mutation display both limb and renal defects. The limb defects, oligodactyly and syndactyly, have been traced to improper differentiation of the apical ectodermal ridge (AER) and shortening of the anteroposterior limb axis. The renal defects, usually aplasia, are thought to result from failure of ureteric bud outgrowth. Since the ld locus gi...

BACKGROUND Sonic hedgehog (Shh), a vertebrate homolog of the Drosophila segment polarity gene hedgehog (hh), has been implicated in patterning of the developing chick limb. Such a role is suggested by the restricted expression of Shh along the posterior limb bud margin, and by the observation that heterologous cells expressing Shh have limb-polarizing activity resembling that of cells from the ...

A major function of the limb bud apical ectodermal ridge (AER) is to produce fibroblast growth factors (FGFs) that signal to the underlying mesenchyme. Previous studies have suggested that of the four FGF genes specifically expressed in the mouse AER, Fgf8 is unique not only in its expression pattern, but also because it is the only such FGF gene that causes limb skeletal abnormalities when ind...

This review represents a compilation of information related to the rodent limb bud culture system from approximately 80 publications after 1969 and conversations with workers in the field. Most of these papers and book chapters refer exclusively to studies with the mouse limb bud. Sections in this review include historical review, end point measurements, activating systems, types of compounds s...

It was shown by Brandt (1944) that phocomelias and atrophied limbs can be produced experimentally after deep implantation of embryonic ectoderm into the primordium of the limb bud in the tail-bud stage (Harrison's stage no. 35) of the amblystoma embryo. The following microscopical analysis of the operated specimens shows some new results which concern the histological changes of the implanted e...

Specification and determination (commitment) of positional identities precedes overt pattern formation during development. In the limb bud, it is clear that the anteroposterior axis is specified at a very early stage and is prepatterned by the mutually antagonistic interaction between Gli3 and Hand2. There is also evidence that the proximodistal axis is specified early and determined progressiv...

IIntroduction I-1. Developmental genes in Drosophila I-2. Skeletal development in human IIDevelopment of the axial skeleton II-1. Signaling molecules involved in the determination of sclerotome to cartilage II2. Role of Hox genes in the regulation of vertebral segments IIIDevelopment of the limbs (appendicular skeleton) III-1. Limb bud differentiation with respect to three axes III-2. Role of F...