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Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000.

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Cover of Developmental Biology

Developmental Biology. 6th edition.

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The Generation of the Dorsal-Ventral Axis

The third axis of the limb distinguishes the dorsal limb (knuckles, nails) from the ventral limb (pads, soles). In 1974, MacCabe and co-workers demonstrated that the dorsal-ventral polarity of the limb bud is determined by the ectoderm encasing it. If the ectoderm is rotated 180° with respect to the limb bud mesenchyme, the dorsal-ventral axis is partially reversed; the distal elements (digits) are “upside down.” This suggested that the late specification of the dorsal-ventral axis of the limb is regulated by its ectodermal component. One molecule that appears to be particularly important in specifying the dorsal-ventral polarity is Wnt7a. The Wnt7a gene is expressed in the dorsal (but not the ventral) ectoderm of the chick and mouse limb buds (Dealy 1993; Parr et al. 1993). In 1995, Parr and McMahon genetically deleted Wnt7a from mouse embryos. The resulting embryos had sole pads on both surfaces of their paws, showing that Wnt7a is needed for the dorsal patterning of the limb (Figure 16.20).

Figure 16.20. Dorsal-to-ventral transformations of limb regions in mice deficient for both Wnt7a genes.

Figure 16.20

Dorsal-to-ventral transformations of limb regions in mice deficient for both Wnt7a genes. (A) Histological section (stained with hemotoxylin and eosin) of wild-type 15.5-day embryonic mouse forelimb paw. The ventral tendons and ventral footpads are readily (more...)

Wnt7a induces activation of the Lmx1 gene in the dorsal mesenchyme, and this gene encodes a transcription factor that appears to be essential for specifying dorsal cell fates in the limb. If this factor is expressed in the ventral mesenchyme cells, they develop a dorsal phenotype (Riddle et al. 1995; Vogel et al. 1995). Mutants of Lmx1 in humans and mice also show its importance for specifying dorsal limb fates. Knockouts of this gene in mice produce a syndrome in which the dorsal limb phenotype is lacking, and loss-of-function mutations in humans produce the nail-patella syndrome, a condition in which the dorsal sides of the limbs have been ventralized (Chen et al. 1998; Dreyer et al. 1998).

By agreement with the publisher, this book is accessible by the search feature, but cannot be browsed.

Copyright © 2000, Sinauer Associates.
Bookshelf ID: NBK10053

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