How to make a zone of polarizing activity

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How to make a zone of polarizing activity: Insights into limb development via the abnormality preaxial polydactyly (Review)

Robert E. Hill

Develop. Growth Differ. (2007) 49, 439–448 | doi: 10.1111/j.1440-169x.2007.00943.x

Early in vertebrate limb development, a program initiates that polarizes the limb along the antero-posterior axis. The mesenchyme at the posterior margin is ultimately responsible for the asymmetry due to a region called the (ZPA). The ZPA produces and secretes the molecule SHH, which coordinates the patterning of the resulting digits. (PPD) is a commonly occurring limb abnormality; investigating the genetic basis of this defect has provided insights into our understanding of digit patterning. PPD disrupts limb asymmetry by producing an ectopic ZPA at the opposite margin of the limb bud. Mutations in the long-range, limb-specific regulatory element of the Shh gene are responsible for the defect. Genetic analysis of this limb abnormality provides an important approach in understanding the mechanisms that control digit patterning.

Key words: , , , , .

Fig. 2.
(A) Composition of the genomic structure around the Shh gene. The position of the ZPA regulatory sequence (ZRS) within the Lmbr1 gene is indicated (yellow oval). The gene desert is indicated and varies in size depending on the species. Regulatory elements identified within the gene desert by Jeong et al. (2006) are also indicated (yellow ovals, marked SBE2-3, and SFPE1). The specificity of ZRS action is shown by the red arrows: the brick patterned rectangles indicate the block to the ZRS for more proximal genes.
(B) Representation of the phenotype caused by abnormal ZRS activity. The first limb to the left is the result of no ZRS activity. The next three limbs represent predictions that would occur with increasing levels of Shh expression (i.e. larger domains of ectopic ZPA). Also represented is triphalangial thumb, which in some cases appears as a transformation of the thumb to the

inger. With increasing ZRS activity the addition of an extra digit is predicted.



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