First published online May 5, 2004
Development 131, 1001e (2004)
© The Company of Biologists Limited
Ten tiny toes
Secreted sonic hedgehog (Shh) signals control digit number and identity in
the developing vertebrate limb. However, the molecular mechanisms that make
thumbs and `pinkies' look different are unclear. On
p. 2339, Chen et al.
report how Gli3 and the Hoxd proteins (both have been previously implicated in
digit development) might be involved in this process, with their finding that
digit pattern is partly regulated by a varying ratio of Gli3 to total Hoxd
protein across the mouse limb bud. Gli3, the intracellular mediator of Shh,
exists in an activator form and a truncated repressor form that shuts off Shh
target gene expression. The researchers identify a genetic and physical
interaction between Gli3 and Hoxd12 (a 5'Hoxd member) that converts the
Gli3 repressor into an activator of Shh targets. Other 5'Hoxd genes are
also expressed differentially across the limb bud. These findings therefore
highlight how the Hoxd proteins might function quantitatively to regulate
digit pattern and identity.
Related articles in Development:
- Direct interaction with Hoxd proteins reverses Gli3-repressor function to promote digit formation downstream of Shh
- Yuting Chen, Vladimir Knezevic, Valerie Ervin, Richard Hutson, Yvona Ward, and Susan Mackem
Development 2004 131: 2339-2347.
[Abstract]
[Full Text]
