Short- and long-range effects of Sonic hedgehog in limb development
AUTOR(ES)
Dillon, Robert
FONTE
National Academy of Sciences
RESUMO
The secreted protein Sonic hedgehog (Shh) and its transmembrane receptor Patched (Ptc) control a major signal transduction pathway in early vertebrate limb development. Ligand-free Ptc interacts with the transmembrane protein Smoothened (Smo) and blocks expression of Smo-controlled genes including ptc. Ligand-bound Ptc removes the block and leads to further expression of ptc, which in turn restricts the range of Shh transport. Currently it is not certain that Shh functions as a morphogen on the 300-μm scale of early chick limb development, because it has been difficult to determine how far different forms of Shh are transported. We develop a model to study the effects of two forms of Shh used experimentally and propose a mechanism for Shh signal transduction based on a two-state model for the Ptc-Smo interaction. Recent bead- and tissue-implant experiments can be explained by using this model without postulating different diffusivities for the two forms of Shh; a difference in other parameters such as the rate of release of Shh from the bead or transplant can explain the results equally well. The model also predicts that lower concentrations of Shh in a bead will produce a response similar to that after a tissue transplant. Our results provide an explanation for the counterintuitive experimental results and show that the same signal transduction mechanism can explain both short- and long-range Shh signaling. We conclude that Shh can function as a long-range morphogen.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=193531Documentos Relacionados
- Respective roles of short- and long-range interactions in protein folding.
- Introduction of short-range restrictions in a protein-folding algorithm involving a long-range geometrical restriction and short-, medium-, and long-range interactions
- Short-range and long-range context effects on coliphage T4 endonuclease II-dependent restriction.
- Model of protein folding: inclusion of short-, medium-, and long-range interactions.
- Long-range electron transfer